SlideShare a Scribd company logo
1 of 41
Download to read offline
Introduction
  To Pharmacokinetics


Pharmacokinetics A Mathematical Tool

           Anas Bahnassi PhD RPh
Lecture Objectives
After completing this lecture, the student will be able
to:
1. Given patient data of the following types, the student will be able to
properly construct a graph and compute the slope using linear
regression: response (R) vs. concentration (C), response (R) vs. time
(T), concentration (C) vs. time (T)
2. Given any two of the above data sets, the student will be able to
compute the slope of the third by linear regression.
3. Give response vs. time and response versus concentration data, the
student will be able to compute the terminal (elimination) rate
constant and half life of the drug.
What is Pharmacokinetics?

      The mathematical description
of drug behavior inside the human body
    It is the study of factors affecting
       the absorption, distribution,
    metabolism and excretion of drug
 As well as the quantitative description
    of how these processes affect the
 time course and intensity of response.
What is Pharmacokinetics?
This powerful mathematical tool is used
to study the drug’s
• Fate in normal and
   pathophysiological conditions
• Distribution / location /penetration
• Clearance / organs
• Conc vs. response
• Bioavailability
• It compares dosage forms and
   different drug brands
• It quantitatively evaluate the
   magnitude of drug interactions
• It provides the basics to make clinical
   predictions
What is Biopharmaceutics?

       How the pharmaceutical formulation
variables affect drug availability and performance
                    (absorption)
                       in vivo
  The use of these information helps optimizing
      therapeutic outcomes of drug products
Distribution

                                                               Elimination

                                           Metabolites
•   IV                       Medication
•   PO                           in
                             Circulation
•   IM
•   MDI          Dosage
                 Regimen
                                                                  Concentration
                                                                   Response
  Route of
Administration



                                                          • Pharmacological
                                                          • Adverse
                                                                       Effect


                           The Pharmacokinetic Process
The Pharmacological Response
                                               Drug must get into
The occupation theory                                blood
The intensity of a pharmacological              and blood is in
response (E) is proportional to the                 contact
concentration of a reversible drug-              with receptor.
        receptor complex

                                    where E is the intensity of the
        ������ ������������������������             pharmacological response, Emax is the
   ������ =                       maximum attainable value of , [D] is the
          ������������ ������              molar concentration of free drug at the
                              active complex and KR is the dissociation
                               constant of the drug-receptor complex.
m:slope               Response vs. Drug
          E=m.lnX+b
                         Concentration
                       X:dose = C.V   V:volume
                                           of
Emax
                                      distribution
The Relationship Between The Administered
    Dose and The Amount of the Drug in The Body
    • The Fraction of the drug reaches the systemic
      circulation is the amount available to elicit
      pharmacologic effect.
    • For iv administration, the amount of drug
      reaches the general circulation is equal to the
      dose administered.
                                      ∞
        ������������������������ = ������0 = (������������������)0 ������������
(AUC)∞0 is the area under curve of plasma drug concentration versus time (AUC) from
                                time zero to time infinity
                     K is the first-order elimination rate constant
                    V (or Vd) is the drug’s volume of distribution.           9
Volume of Distribution
“The apparent volume into which a given mass
of drug would need to be diluted in order to give
the observed concentration.”

                                              ������
                                         ������ =
                                              ������


    Basic Pharmacokinetics: S. Jambhekar , Phillip Breen 2009
                                         Anas Bahnassi PhD 2011   10
The Relationship Between The
Administered Dose and The Amount of the
Drug in The Body
For the extravascular route, the amount of
drug that reaches general circulation is the
product of the bioavailable fraction (F) and
the dose administered.

                                         ∞
  ������. ������������������������ = ������������0 =         (������������������)0 ������������

                 Anas Bahnassi PhD 2011           11
Min. Toxic Conc.




                                                 Min. Effective Conc.




Previous equations suggest that we must know or determine
all the parameters (i.e. AUC, 0 , K, V, F) for a given drug;
therefore, it is important to know the concentration of a drug
in blood (plasma or serum) and/or the amount (mass) of drug
removed in urine (excretion data).
                        Anas Bahnassi PhD 2011                   12
Onset of Action:
The time at which the administered drug reaches the therapeutic range
                    and begins to produce effect.


                       Therapeutic Range:
 The plasma or serum concentration range within which the drug is
         likely to produce the therapeutic activity or effect

                       Duration of Action:
    The time span from the beginning of the onset of action up to
                      termination of action

                     Termination of Action:
  The time at which the drug concentration in plasma falls below the
                  minimum effective concentration

                          Anas Bahnassi PhD 2011                    13
Amount of Drug in the Urine




           Anas Bahnassi PhD 2011   14
Sites of Drug Administration
                                          1. There is no absorption
                                                     phase.
                           Intra-           2. There is immediate
Intravascular              venous               onset of action.
                                         3. The entire administered
   Routes                                     dose is available to
                           Intra-        produce pharmacological
                          arterial                  effects.
                                         4. This route is used more
                                           often in life-threatening
                                                  situations.
                                          5. Adverse reactions are
                                            difficult to reverse or
                                             control; accuracy in
                                               calculations and
                                           administration of drug
                Anas Bahnassi PhD 2011    dose, therefore, are very
                                                               15

                                                    critical.
Sites of Drug Administration
                   Oral
 Inhalation
                                    Intra-
                                   mascular

                  Extra-
                 vascular                Sub-
Rectal                                 cutaneous


         Trans-               Sub-
         dermal             lingual
              Anas Bahnassi PhD 2011               16
Important Features of
                             Extravascular Routes




                   1. An absorption phase is present.
2. The onset of action is determined by factors such as formulation and
 type of dosage form, route of administration, physicochemical properties
                of drugs and other physiological variables.
  3. The entire administered dose of a drug may not always reach the
              general circulation (i.e. incomplete absorption).
                          Anas Bahnassi PhD 2011                   17
Review of the ADME Process
               • The process by which a drug proceeds from
Absorption       the site of administration to the site of
                 measurement


               • the process of reversible transfer of drug to
Distribution     and from the site of measurement



               • the process of a conversion of one chemical
Metabolism       species to another chemical species


               • The irreversible loss of drug from the site of
Elimination      measurement. It may occur by metabolism
                 or excretion.
                 Anas Bahnassi PhD 2011                           18
Excretion                                  Disposition
The irreversible loss of          Once a drug is in the systemic,
a drug in a chemically            it is distributed simultaneously
unchanged or unaltered            to all tissues including the organ
form.                             responsible for its elimination.




                   Anas Bahnassi PhD 2011                       19
Pharmacokinetic Models




The change in drug’s concentration after administration can be described
using certain equations mostly exponential. This suggests that ADME
processes follow a first order process and therefore drug transport is
mediated through passive diffusion mechanism. This means that there is a
direct relationship between the plasma concentration of the drug and the
amount eliminated in the urine and the original administered dose. This
identifies the term Linear Pharmacokinetics.
                           Anas Bahnassi PhD 2011                 20
Compartment Concept in PK

• It is necessary to describe the pharmacokinetic
  parameters adequately and accurately.
• The selection of the compartment model
  depends solely on the distribution
  characteristics of the drug administered.
• The corresponding equation depends on the
  compartment model and the route of
  administration.


                  Anas Bahnassi PhD 2011        21
The model selection process is highly
        dependent upon the following factors.
1.    The frequency at which plasma samples are collected. It is
      highly recommended that plasma samples are collected as
      early as possible, particularly for first couple of hours,
      following the administration of the dose of a drug.
2.    The sensitivity of the procedure employed to analyze drug
      concentration in plasma samples. (Since inflections of the
      plasma concentration versus time curve in the low
      concentration regions may not be detected when using assays
      with poor sensitivity, the use of a more sensitive analytical
      procedure will increase the probability of choosing the correct
      compartment model.)
3.    The physicochemical properties (e.g. the lipophilicity)of a
      drug.



     Basic Pharmacokinetics: S. Jambhekar , Phillip Breen 2009
                                          Anas Bahnassi PhD 2011   22
Pharmacokinetic
                         Models




Anas Bahnassi PhD 2011            23
IV Bolus Dose - One
                                                                Compartment
Considering the body to
behave      as     a    single
compartment. In order to
simplify the mathematics it
is often possible to assume
that a drug given by rapid
intravenous injection, a
bolus, is rapidly mixed. This
figure      represents     the
uniformly mixed drug very
shortly after administration.

   Niazi, S. 1979 Textbook of Biopharmaceutics and Clinical Pharmacokinetics, Appleton-Century-Crofts, New York, p142
                                            Anas Bahnassi PhD 2011                                                24
IV Bolus Dose - One
                                                                       Compartment

            ������ = ������0 ������ −������������ = ������������ −������������ 1

        ������������������ = ������������������ − ������������ (2)

                             E=m.lnX+b
    ������ − ������ ������0 − ������
           =         ������������ (3)
       ������      ������

                             E=E0-Rt
Basic Pharmacokinetics REV. 99.4.25 3-4 1996-1999 Michael C. Makoid
          Niazi, S. 1979 Textbook of Biopharmaceutics and Clinical Pharmacokinetics, Appleton-Century-Crofts, New York, p142
                                                   Anas Bahnassi PhD 2011                                                25
IV Bolus Two
                                                     Compartment Model
Often a one compartment model is not sufficient to represent the
pharmacokinetics of a drug. A two compartment model often has
wider application. Here we consider the body is a central
compartment with rapid mixing and a peripheral compartment
with slower distribution.
The central compartment
is uniformly mixed very
shortly     after    drug
administration, whereas
it takes some time for the
peripheral compartment
to reach a pseudo
equilibrium.
Niazi, S. 1979 Textbook of Biopharmaceutics and
 Clinical Pharmacokinetics, Appleton-Century-
            Crofts, New York, p175l.;l
                                            Anas Bahnassi PhD 2011   26
Semi-log Graph




Rapid Distribution                       Slow Distribution

                     Anas Bahnassi PhD 2011                  27
Absorption and Elimination




One Compartment with                            Two Compartment with
  absorption phase      Semi-log Graph            absorption phase
                                                                   28

                       Anas Bahnassi PhD 2011
Anas Bahnassi PhD 2011   29
A basic model for absorption and
                              Disposition
  The model is based on mass
     balance considerations:
                                                 At any time t, for the
  1. The amount (e.g. mg) of
                                                  extravascular route:
         unchanged drug and/or
                                            F(Dose) = absorbable amount at
   metabolite(s) can be measured in
                                           the absorption site + amount in the
                  urine.
                                               body + cumulative amount
2. Drug and metabolite(s) in the
                                           metabolized + cumulative amount
    body (blood, plasma or serum)
                                                   excreted unchanged
     are measured in concentration
          units (e.g. μgmL-1).
                                              For the intravascular route:
3. Direct measurement of drug at
                                              Dose = amount in the body +
      the site of administration is
                                            amount metabolized + cumulative
    impractical; however, it can be
                                              amount excreted unchanged:
           assessed indirectly.

                          Anas Bahnassi PhD 2011                         30
Characteristics of One
                             Compartment Model
   1. Equilibrium between drug concentrations in
      different tissues or organs is obtained rapidly
    (virtually instantaneously), following drug input.
    Therefore, a distinction between distribution and
            elimination phases is not possible.
2. The amount (mass) of drug distributed in different
                  tissues may be different.
3. Following equilibrium, changes in drug concentra-
      tion in blood (which can be sampled) reflect
    changes in concentration of drug in other tissues
                (which cannot be sampled).
                      Anas Bahnassi PhD 2011         31
Drug Concentration versus Time




From a graph such as this we can see the relationship between drug
  concentration and drug effect. If a drug has to reach an effective
 concentration at a receptor site this will be reflected as a required
                        blood concentration.
      Barr, W.H. 1968 Principles of        Anas Bahnassi PhD 2011   32
biopharmaceutics, Amer. J. Pharm. Ed., 32,
                   958
Drug Product Performance
                                                 Parameters
                                                                     The figure shows
                                                                     some of the bio-
                                                                       pharmaceutic
                                                                        parameters
                                                                       which can be
                                                                     used to measure
                                                                       drug product
                                                                       performance.
                                                                        Later in the
                                                                     semester we will
                                                                       use the trap-
                                                                      ezoidal method
Dittert, L.W. and DiSanto, A.R. 1973 The bioavailability of drug
                                                                       of calculating
         products, J. Amer. Pharm. Assoc., NS13, 421-432                   AUC.
                                            Anas Bahnassi PhD 2011              33
Rate Processes

 After administration, the drug
    is subject to a number of
processes (ADME) whose rates
  control the concentration of
    drug in the elusive region
   known as ‘‘site of action.’’
These processes affect the onset
of action, as well as the duration
         and intensity of
   pharmacological response.
                      Anas Bahnassi PhD 2011             34
Zero-order Process
                                              Applications of zero-
                                             order processes include
                                               administration of a
                                             drug as an intravenous
                                              infusion, formulation
                                             and administration of a
                                                  drug through
                                                controlled release
                                                dosage forms and
                                             administration of drugs
                                              through trans-dermal
                                             drug delivery systems.


                    Anas Bahnassi PhD 2011                    35
Rectilinear Paper
First-order Process




                         Rectilinear Paper

Anas Bahnassi PhD 2011                  36
First-order Process


                          -dX/dt xX-1 =K,
                          where units are
                            mgh-1 x mg-1
                          K has unit is: h-1.




                         Rectilinear Paper
Anas Bahnassi PhD 2011                   37
First-order Process




                         Rectilinear Paper
Anas Bahnassi PhD 2011                  38
First-order Process



Rectilinear Paper                      Semilogarithmic
                                           Paper




              Anas Bahnassi PhD 2011                39
Comparison of Zero & First order
    processes

Term       Zero order                     First order
-dx/dt     = K0 Rate remains              KX Rate changes over time
           constant
Rate       =K0                            =K
constant   unit = mgh-1                   unit=h-1
X          X=X0-Kt                        lnX=lnX0-Kt or
                                          logX=logX0-kt/2.303




                          Anas Bahnassi PhD 2011                      40
Pharmacokinetics

Anas Bahnassi PhD RPh


                                abahnassi@gmail.com

   http://www.linkedin.com/pub/anas-bahnassi/8/707/693
                        http://bahnassi.coursesites.com

              attribution – non-commercial – share alike

More Related Content

What's hot

Rectal drug delivery system [RDDS]
Rectal drug delivery system [RDDS]Rectal drug delivery system [RDDS]
Rectal drug delivery system [RDDS]Sagar Savale
 
Clinical Pharmacokinetics
Clinical PharmacokineticsClinical Pharmacokinetics
Clinical PharmacokineticsNausheen Fatima
 
Seminar on pharmacokinetic parameters of two compartment open model
Seminar on pharmacokinetic parameters of two compartment open modelSeminar on pharmacokinetic parameters of two compartment open model
Seminar on pharmacokinetic parameters of two compartment open modelDivya Singh
 
Physiological pharmacokinetic models
Physiological pharmacokinetic modelsPhysiological pharmacokinetic models
Physiological pharmacokinetic modelsSanjay Yadav
 
Area under the curve- Dr ASHWIN R
Area under the curve- Dr ASHWIN RArea under the curve- Dr ASHWIN R
Area under the curve- Dr ASHWIN Rashwin ravi
 
Bioavailability and bioequivalence
Bioavailability and bioequivalenceBioavailability and bioequivalence
Bioavailability and bioequivalenceNaresh Gorantla
 
Dose adjustment in renal disease
Dose adjustment in renal diseaseDose adjustment in renal disease
Dose adjustment in renal diseaseAreej Abu Hanieh
 
Estimation of pharmacokinetic parameters
Estimation of pharmacokinetic parametersEstimation of pharmacokinetic parameters
Estimation of pharmacokinetic parametersKarun Kumar
 
Multiple Dosage Oral Administration/ Dosage Regimen
Multiple Dosage Oral Administration/ Dosage Regimen Multiple Dosage Oral Administration/ Dosage Regimen
Multiple Dosage Oral Administration/ Dosage Regimen Nausheen Fatima
 
Gastrointestinal absorption of drugs
Gastrointestinal absorption of drugsGastrointestinal absorption of drugs
Gastrointestinal absorption of drugsSiddu K M
 
Expt. 13 Calculation of pharmacokinetic parameters from a given data
Expt. 13 Calculation of pharmacokinetic parameters from a given dataExpt. 13 Calculation of pharmacokinetic parameters from a given data
Expt. 13 Calculation of pharmacokinetic parameters from a given dataVISHALJADHAV100
 
Effects of liver diseases on pharmacokinetics
Effects of liver diseases on pharmacokineticsEffects of liver diseases on pharmacokinetics
Effects of liver diseases on pharmacokineticsDr. Ramesh Bhandari
 
Biopharmaceutics
BiopharmaceuticsBiopharmaceutics
BiopharmaceuticsSa Na
 
Introduction to biopharmaceutics
Introduction to biopharmaceuticsIntroduction to biopharmaceutics
Introduction to biopharmaceuticsSuvarta Maru
 

What's hot (20)

Pharmacokinetic models
Pharmacokinetic modelsPharmacokinetic models
Pharmacokinetic models
 
Rectal drug delivery system [RDDS]
Rectal drug delivery system [RDDS]Rectal drug delivery system [RDDS]
Rectal drug delivery system [RDDS]
 
Umesh
UmeshUmesh
Umesh
 
Clinical Pharmacokinetics
Clinical PharmacokineticsClinical Pharmacokinetics
Clinical Pharmacokinetics
 
Seminar on pharmacokinetic parameters of two compartment open model
Seminar on pharmacokinetic parameters of two compartment open modelSeminar on pharmacokinetic parameters of two compartment open model
Seminar on pharmacokinetic parameters of two compartment open model
 
Drug interactions
Drug interactionsDrug interactions
Drug interactions
 
Physiological pharmacokinetic models
Physiological pharmacokinetic modelsPhysiological pharmacokinetic models
Physiological pharmacokinetic models
 
Area under the curve- Dr ASHWIN R
Area under the curve- Dr ASHWIN RArea under the curve- Dr ASHWIN R
Area under the curve- Dr ASHWIN R
 
Bioavailability and bioequivalence
Bioavailability and bioequivalenceBioavailability and bioequivalence
Bioavailability and bioequivalence
 
Multiple Dosage regimen
Multiple Dosage regimenMultiple Dosage regimen
Multiple Dosage regimen
 
Dose adjustment in renal disease
Dose adjustment in renal diseaseDose adjustment in renal disease
Dose adjustment in renal disease
 
Estimation of pharmacokinetic parameters
Estimation of pharmacokinetic parametersEstimation of pharmacokinetic parameters
Estimation of pharmacokinetic parameters
 
Bio availability and bio equivalence
Bio availability and bio equivalenceBio availability and bio equivalence
Bio availability and bio equivalence
 
Multiple Dosage Oral Administration/ Dosage Regimen
Multiple Dosage Oral Administration/ Dosage Regimen Multiple Dosage Oral Administration/ Dosage Regimen
Multiple Dosage Oral Administration/ Dosage Regimen
 
Adme
AdmeAdme
Adme
 
Gastrointestinal absorption of drugs
Gastrointestinal absorption of drugsGastrointestinal absorption of drugs
Gastrointestinal absorption of drugs
 
Expt. 13 Calculation of pharmacokinetic parameters from a given data
Expt. 13 Calculation of pharmacokinetic parameters from a given dataExpt. 13 Calculation of pharmacokinetic parameters from a given data
Expt. 13 Calculation of pharmacokinetic parameters from a given data
 
Effects of liver diseases on pharmacokinetics
Effects of liver diseases on pharmacokineticsEffects of liver diseases on pharmacokinetics
Effects of liver diseases on pharmacokinetics
 
Biopharmaceutics
BiopharmaceuticsBiopharmaceutics
Biopharmaceutics
 
Introduction to biopharmaceutics
Introduction to biopharmaceuticsIntroduction to biopharmaceutics
Introduction to biopharmaceutics
 

Similar to Pharmacokinetics: Lecture One

Bioavailability by pradip
Bioavailability by pradipBioavailability by pradip
Bioavailability by pradipPradip Ghori
 
BioavailabilityandBioequivalence.pdf
BioavailabilityandBioequivalence.pdfBioavailabilityandBioequivalence.pdf
BioavailabilityandBioequivalence.pdfabhisheksinghcompute
 
Methods For Assesment Of Bioavailability
Methods For Assesment Of Bioavailability Methods For Assesment Of Bioavailability
Methods For Assesment Of Bioavailability Anindya Jana
 
BIO AVAILABILITY & Bio equivalence.pptx
BIO AVAILABILITY & Bio equivalence.pptxBIO AVAILABILITY & Bio equivalence.pptx
BIO AVAILABILITY & Bio equivalence.pptxMANSISONI146297
 
Drug Bio-availability.pdf
Drug Bio-availability.pdfDrug Bio-availability.pdf
Drug Bio-availability.pdfIshaGumber1
 
-Bioavailability and Bioequivalence-.pdf
-Bioavailability and Bioequivalence-.pdf-Bioavailability and Bioequivalence-.pdf
-Bioavailability and Bioequivalence-.pdfAshwin Saxena
 
Bioavailability and bioequivalence of Drug Product.docx
Bioavailability and bioequivalence of Drug Product.docxBioavailability and bioequivalence of Drug Product.docx
Bioavailability and bioequivalence of Drug Product.docxabhisheksinghcompute
 
bioavailability & bioequivalence
bioavailability & bioequivalence bioavailability & bioequivalence
bioavailability & bioequivalence BINDIYA PATEL
 
Acs0823 Clinical Pharmacology
Acs0823 Clinical PharmacologyAcs0823 Clinical Pharmacology
Acs0823 Clinical Pharmacologymedbookonline
 
Drug product performance
Drug product performanceDrug product performance
Drug product performanceVivekBihania
 
Bioavailability , absolute bioavalability, relative bioavailability, Purpose ...
Bioavailability , absolute bioavalability, relative bioavailability, Purpose ...Bioavailability , absolute bioavalability, relative bioavailability, Purpose ...
Bioavailability , absolute bioavalability, relative bioavailability, Purpose ...Manikant Prasad Shah
 
Applications of pharmacokinetics in new drug development,dosage form design &...
Applications of pharmacokinetics in new drug development,dosage form design &...Applications of pharmacokinetics in new drug development,dosage form design &...
Applications of pharmacokinetics in new drug development,dosage form design &...Malla Reddy College of Pharmacy
 
Pharmacokinetics / Biopharmaceutics - Bioavailability and Bioequivalence
Pharmacokinetics / Biopharmaceutics - Bioavailability and BioequivalencePharmacokinetics / Biopharmaceutics - Bioavailability and Bioequivalence
Pharmacokinetics / Biopharmaceutics - Bioavailability and BioequivalenceAreej Abu Hanieh
 
Bioavailability
BioavailabilityBioavailability
BioavailabilityUOP
 

Similar to Pharmacokinetics: Lecture One (20)

Bioavailability by pradip
Bioavailability by pradipBioavailability by pradip
Bioavailability by pradip
 
Bioavailabilityand bioequivalence
Bioavailabilityand bioequivalenceBioavailabilityand bioequivalence
Bioavailabilityand bioequivalence
 
BioavailabilityandBioequivalence.pdf
BioavailabilityandBioequivalence.pdfBioavailabilityandBioequivalence.pdf
BioavailabilityandBioequivalence.pdf
 
Methods For Assesment Of Bioavailability
Methods For Assesment Of Bioavailability Methods For Assesment Of Bioavailability
Methods For Assesment Of Bioavailability
 
BIO AVAILABILITY & Bio equivalence.pptx
BIO AVAILABILITY & Bio equivalence.pptxBIO AVAILABILITY & Bio equivalence.pptx
BIO AVAILABILITY & Bio equivalence.pptx
 
GP-Bioavailability.pdf
GP-Bioavailability.pdfGP-Bioavailability.pdf
GP-Bioavailability.pdf
 
Drug Bio-availability.pdf
Drug Bio-availability.pdfDrug Bio-availability.pdf
Drug Bio-availability.pdf
 
-Bioavailability and Bioequivalence-.pdf
-Bioavailability and Bioequivalence-.pdf-Bioavailability and Bioequivalence-.pdf
-Bioavailability and Bioequivalence-.pdf
 
Bioavailability and bioequivalence of Drug Product.docx
Bioavailability and bioequivalence of Drug Product.docxBioavailability and bioequivalence of Drug Product.docx
Bioavailability and bioequivalence of Drug Product.docx
 
bioavailability & bioequivalence
bioavailability & bioequivalence bioavailability & bioequivalence
bioavailability & bioequivalence
 
Drug levels in blood
Drug levels in blood Drug levels in blood
Drug levels in blood
 
Pharmacokinetics
PharmacokineticsPharmacokinetics
Pharmacokinetics
 
What is a drug
What is a drugWhat is a drug
What is a drug
 
Acs0823 Clinical Pharmacology
Acs0823 Clinical PharmacologyAcs0823 Clinical Pharmacology
Acs0823 Clinical Pharmacology
 
Drug product performance
Drug product performanceDrug product performance
Drug product performance
 
Bioavailability , absolute bioavalability, relative bioavailability, Purpose ...
Bioavailability , absolute bioavalability, relative bioavailability, Purpose ...Bioavailability , absolute bioavalability, relative bioavailability, Purpose ...
Bioavailability , absolute bioavalability, relative bioavailability, Purpose ...
 
Bioavailability
BioavailabilityBioavailability
Bioavailability
 
Applications of pharmacokinetics in new drug development,dosage form design &...
Applications of pharmacokinetics in new drug development,dosage form design &...Applications of pharmacokinetics in new drug development,dosage form design &...
Applications of pharmacokinetics in new drug development,dosage form design &...
 
Pharmacokinetics / Biopharmaceutics - Bioavailability and Bioequivalence
Pharmacokinetics / Biopharmaceutics - Bioavailability and BioequivalencePharmacokinetics / Biopharmaceutics - Bioavailability and Bioequivalence
Pharmacokinetics / Biopharmaceutics - Bioavailability and Bioequivalence
 
Bioavailability
BioavailabilityBioavailability
Bioavailability
 

More from Anas Bahnassi أنس البهنسي

Pharmacy Practice: Lecture one: Medication Management Cycle Part One
Pharmacy Practice: Lecture one: Medication Management Cycle Part OnePharmacy Practice: Lecture one: Medication Management Cycle Part One
Pharmacy Practice: Lecture one: Medication Management Cycle Part OneAnas Bahnassi أنس البهنسي
 

More from Anas Bahnassi أنس البهنسي (20)

Lecture nine cardiovascular_emeregencies
Lecture nine cardiovascular_emeregenciesLecture nine cardiovascular_emeregencies
Lecture nine cardiovascular_emeregencies
 
Urinary Tract Infections
Urinary Tract InfectionsUrinary Tract Infections
Urinary Tract Infections
 
Pneumonia
PneumoniaPneumonia
Pneumonia
 
Influenza
InfluenzaInfluenza
Influenza
 
Acute bronchitis
Acute bronchitisAcute bronchitis
Acute bronchitis
 
Sinusitis
SinusitisSinusitis
Sinusitis
 
Streptococccal sore throat
Streptococccal sore throatStreptococccal sore throat
Streptococccal sore throat
 
Acute Otitis Media
Acute Otitis Media Acute Otitis Media
Acute Otitis Media
 
Principles of infectious diseases
Principles of infectious diseasesPrinciples of infectious diseases
Principles of infectious diseases
 
Lecture three management cycle Part 3
Lecture three management cycle Part 3Lecture three management cycle Part 3
Lecture three management cycle Part 3
 
Lecture two management cycle Part: 2
Lecture two management cycle Part: 2Lecture two management cycle Part: 2
Lecture two management cycle Part: 2
 
Pharmacy Practice: Lecture one: Medication Management Cycle Part One
Pharmacy Practice: Lecture one: Medication Management Cycle Part OnePharmacy Practice: Lecture one: Medication Management Cycle Part One
Pharmacy Practice: Lecture one: Medication Management Cycle Part One
 
Osteoarthritis
OsteoarthritisOsteoarthritis
Osteoarthritis
 
Juvenile idiopathic arthritis
Juvenile idiopathic arthritisJuvenile idiopathic arthritis
Juvenile idiopathic arthritis
 
Rheumatoid arthritis Part 2
Rheumatoid arthritis Part 2Rheumatoid arthritis Part 2
Rheumatoid arthritis Part 2
 
Rheumatoid Arthritis Part !
Rheumatoid Arthritis Part !Rheumatoid Arthritis Part !
Rheumatoid Arthritis Part !
 
Pharmacotherapy of Diabetes: Part 2
Pharmacotherapy of Diabetes: Part 2Pharmacotherapy of Diabetes: Part 2
Pharmacotherapy of Diabetes: Part 2
 
Role of community pharmacists in diabetes management
Role of community pharmacists in diabetes managementRole of community pharmacists in diabetes management
Role of community pharmacists in diabetes management
 
Diabetes Care: Part One
Diabetes Care: Part OneDiabetes Care: Part One
Diabetes Care: Part One
 
Premixed insulin dosing in actual practice
Premixed insulin dosing in actual practicePremixed insulin dosing in actual practice
Premixed insulin dosing in actual practice
 

Recently uploaded

General views of Histopathology and step
General views of Histopathology and stepGeneral views of Histopathology and step
General views of Histopathology and stepobaje godwin sunday
 
Human-AI Co-Creation of Worked Examples for Programming Classes
Human-AI Co-Creation of Worked Examples for Programming ClassesHuman-AI Co-Creation of Worked Examples for Programming Classes
Human-AI Co-Creation of Worked Examples for Programming ClassesMohammad Hassany
 
Easter in the USA presentation by Chloe.
Easter in the USA presentation by Chloe.Easter in the USA presentation by Chloe.
Easter in the USA presentation by Chloe.EnglishCEIPdeSigeiro
 
Patient Counselling. Definition of patient counseling; steps involved in pati...
Patient Counselling. Definition of patient counseling; steps involved in pati...Patient Counselling. Definition of patient counseling; steps involved in pati...
Patient Counselling. Definition of patient counseling; steps involved in pati...raviapr7
 
How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17Celine George
 
CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...
CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...
CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...Nguyen Thanh Tu Collection
 
How to Solve Singleton Error in the Odoo 17
How to Solve Singleton Error in the  Odoo 17How to Solve Singleton Error in the  Odoo 17
How to Solve Singleton Error in the Odoo 17Celine George
 
In - Vivo and In - Vitro Correlation.pptx
In - Vivo and In - Vitro Correlation.pptxIn - Vivo and In - Vitro Correlation.pptx
In - Vivo and In - Vitro Correlation.pptxAditiChauhan701637
 
Patterns of Written Texts Across Disciplines.pptx
Patterns of Written Texts Across Disciplines.pptxPatterns of Written Texts Across Disciplines.pptx
Patterns of Written Texts Across Disciplines.pptxMYDA ANGELICA SUAN
 
Clinical Pharmacy Introduction to Clinical Pharmacy, Concept of clinical pptx
Clinical Pharmacy  Introduction to Clinical Pharmacy, Concept of clinical pptxClinical Pharmacy  Introduction to Clinical Pharmacy, Concept of clinical pptx
Clinical Pharmacy Introduction to Clinical Pharmacy, Concept of clinical pptxraviapr7
 
How to Make a Field read-only in Odoo 17
How to Make a Field read-only in Odoo 17How to Make a Field read-only in Odoo 17
How to Make a Field read-only in Odoo 17Celine George
 
DUST OF SNOW_BY ROBERT FROST_EDITED BY_ TANMOY MISHRA
DUST OF SNOW_BY ROBERT FROST_EDITED BY_ TANMOY MISHRADUST OF SNOW_BY ROBERT FROST_EDITED BY_ TANMOY MISHRA
DUST OF SNOW_BY ROBERT FROST_EDITED BY_ TANMOY MISHRATanmoy Mishra
 
Practical Research 1 Lesson 9 Scope and delimitation.pptx
Practical Research 1 Lesson 9 Scope and delimitation.pptxPractical Research 1 Lesson 9 Scope and delimitation.pptx
Practical Research 1 Lesson 9 Scope and delimitation.pptxKatherine Villaluna
 
How to Add Existing Field in One2Many Tree View in Odoo 17
How to Add Existing Field in One2Many Tree View in Odoo 17How to Add Existing Field in One2Many Tree View in Odoo 17
How to Add Existing Field in One2Many Tree View in Odoo 17Celine George
 
Benefits & Challenges of Inclusive Education
Benefits & Challenges of Inclusive EducationBenefits & Challenges of Inclusive Education
Benefits & Challenges of Inclusive EducationMJDuyan
 
5 charts on South Africa as a source country for international student recrui...
5 charts on South Africa as a source country for international student recrui...5 charts on South Africa as a source country for international student recrui...
5 charts on South Africa as a source country for international student recrui...CaraSkikne1
 
Education and training program in the hospital APR.pptx
Education and training program in the hospital APR.pptxEducation and training program in the hospital APR.pptx
Education and training program in the hospital APR.pptxraviapr7
 
Quality Assurance_GOOD LABORATORY PRACTICE
Quality Assurance_GOOD LABORATORY PRACTICEQuality Assurance_GOOD LABORATORY PRACTICE
Quality Assurance_GOOD LABORATORY PRACTICESayali Powar
 

Recently uploaded (20)

General views of Histopathology and step
General views of Histopathology and stepGeneral views of Histopathology and step
General views of Histopathology and step
 
Personal Resilience in Project Management 2 - TV Edit 1a.pdf
Personal Resilience in Project Management 2 - TV Edit 1a.pdfPersonal Resilience in Project Management 2 - TV Edit 1a.pdf
Personal Resilience in Project Management 2 - TV Edit 1a.pdf
 
Human-AI Co-Creation of Worked Examples for Programming Classes
Human-AI Co-Creation of Worked Examples for Programming ClassesHuman-AI Co-Creation of Worked Examples for Programming Classes
Human-AI Co-Creation of Worked Examples for Programming Classes
 
Easter in the USA presentation by Chloe.
Easter in the USA presentation by Chloe.Easter in the USA presentation by Chloe.
Easter in the USA presentation by Chloe.
 
Patient Counselling. Definition of patient counseling; steps involved in pati...
Patient Counselling. Definition of patient counseling; steps involved in pati...Patient Counselling. Definition of patient counseling; steps involved in pati...
Patient Counselling. Definition of patient counseling; steps involved in pati...
 
How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17
 
CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...
CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...
CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...
 
How to Solve Singleton Error in the Odoo 17
How to Solve Singleton Error in the  Odoo 17How to Solve Singleton Error in the  Odoo 17
How to Solve Singleton Error in the Odoo 17
 
In - Vivo and In - Vitro Correlation.pptx
In - Vivo and In - Vitro Correlation.pptxIn - Vivo and In - Vitro Correlation.pptx
In - Vivo and In - Vitro Correlation.pptx
 
Patterns of Written Texts Across Disciplines.pptx
Patterns of Written Texts Across Disciplines.pptxPatterns of Written Texts Across Disciplines.pptx
Patterns of Written Texts Across Disciplines.pptx
 
Finals of Kant get Marx 2.0 : a general politics quiz
Finals of Kant get Marx 2.0 : a general politics quizFinals of Kant get Marx 2.0 : a general politics quiz
Finals of Kant get Marx 2.0 : a general politics quiz
 
Clinical Pharmacy Introduction to Clinical Pharmacy, Concept of clinical pptx
Clinical Pharmacy  Introduction to Clinical Pharmacy, Concept of clinical pptxClinical Pharmacy  Introduction to Clinical Pharmacy, Concept of clinical pptx
Clinical Pharmacy Introduction to Clinical Pharmacy, Concept of clinical pptx
 
How to Make a Field read-only in Odoo 17
How to Make a Field read-only in Odoo 17How to Make a Field read-only in Odoo 17
How to Make a Field read-only in Odoo 17
 
DUST OF SNOW_BY ROBERT FROST_EDITED BY_ TANMOY MISHRA
DUST OF SNOW_BY ROBERT FROST_EDITED BY_ TANMOY MISHRADUST OF SNOW_BY ROBERT FROST_EDITED BY_ TANMOY MISHRA
DUST OF SNOW_BY ROBERT FROST_EDITED BY_ TANMOY MISHRA
 
Practical Research 1 Lesson 9 Scope and delimitation.pptx
Practical Research 1 Lesson 9 Scope and delimitation.pptxPractical Research 1 Lesson 9 Scope and delimitation.pptx
Practical Research 1 Lesson 9 Scope and delimitation.pptx
 
How to Add Existing Field in One2Many Tree View in Odoo 17
How to Add Existing Field in One2Many Tree View in Odoo 17How to Add Existing Field in One2Many Tree View in Odoo 17
How to Add Existing Field in One2Many Tree View in Odoo 17
 
Benefits & Challenges of Inclusive Education
Benefits & Challenges of Inclusive EducationBenefits & Challenges of Inclusive Education
Benefits & Challenges of Inclusive Education
 
5 charts on South Africa as a source country for international student recrui...
5 charts on South Africa as a source country for international student recrui...5 charts on South Africa as a source country for international student recrui...
5 charts on South Africa as a source country for international student recrui...
 
Education and training program in the hospital APR.pptx
Education and training program in the hospital APR.pptxEducation and training program in the hospital APR.pptx
Education and training program in the hospital APR.pptx
 
Quality Assurance_GOOD LABORATORY PRACTICE
Quality Assurance_GOOD LABORATORY PRACTICEQuality Assurance_GOOD LABORATORY PRACTICE
Quality Assurance_GOOD LABORATORY PRACTICE
 

Pharmacokinetics: Lecture One

  • 1. Introduction To Pharmacokinetics Pharmacokinetics A Mathematical Tool Anas Bahnassi PhD RPh
  • 2. Lecture Objectives After completing this lecture, the student will be able to: 1. Given patient data of the following types, the student will be able to properly construct a graph and compute the slope using linear regression: response (R) vs. concentration (C), response (R) vs. time (T), concentration (C) vs. time (T) 2. Given any two of the above data sets, the student will be able to compute the slope of the third by linear regression. 3. Give response vs. time and response versus concentration data, the student will be able to compute the terminal (elimination) rate constant and half life of the drug.
  • 3. What is Pharmacokinetics? The mathematical description of drug behavior inside the human body It is the study of factors affecting the absorption, distribution, metabolism and excretion of drug As well as the quantitative description of how these processes affect the time course and intensity of response.
  • 4. What is Pharmacokinetics? This powerful mathematical tool is used to study the drug’s • Fate in normal and pathophysiological conditions • Distribution / location /penetration • Clearance / organs • Conc vs. response • Bioavailability • It compares dosage forms and different drug brands • It quantitatively evaluate the magnitude of drug interactions • It provides the basics to make clinical predictions
  • 5. What is Biopharmaceutics? How the pharmaceutical formulation variables affect drug availability and performance (absorption) in vivo The use of these information helps optimizing therapeutic outcomes of drug products
  • 6. Distribution Elimination Metabolites • IV Medication • PO in Circulation • IM • MDI Dosage Regimen Concentration Response Route of Administration • Pharmacological • Adverse Effect The Pharmacokinetic Process
  • 7. The Pharmacological Response Drug must get into The occupation theory blood The intensity of a pharmacological and blood is in response (E) is proportional to the contact concentration of a reversible drug- with receptor. receptor complex where E is the intensity of the ������ ������������������������ pharmacological response, Emax is the ������ = maximum attainable value of , [D] is the ������������ ������ molar concentration of free drug at the active complex and KR is the dissociation constant of the drug-receptor complex.
  • 8. m:slope Response vs. Drug E=m.lnX+b Concentration X:dose = C.V V:volume of Emax distribution
  • 9. The Relationship Between The Administered Dose and The Amount of the Drug in The Body • The Fraction of the drug reaches the systemic circulation is the amount available to elicit pharmacologic effect. • For iv administration, the amount of drug reaches the general circulation is equal to the dose administered. ∞ ������������������������ = ������0 = (������������������)0 ������������ (AUC)∞0 is the area under curve of plasma drug concentration versus time (AUC) from time zero to time infinity K is the first-order elimination rate constant V (or Vd) is the drug’s volume of distribution. 9
  • 10. Volume of Distribution “The apparent volume into which a given mass of drug would need to be diluted in order to give the observed concentration.” ������ ������ = ������ Basic Pharmacokinetics: S. Jambhekar , Phillip Breen 2009 Anas Bahnassi PhD 2011 10
  • 11. The Relationship Between The Administered Dose and The Amount of the Drug in The Body For the extravascular route, the amount of drug that reaches general circulation is the product of the bioavailable fraction (F) and the dose administered. ∞ ������. ������������������������ = ������������0 = (������������������)0 ������������ Anas Bahnassi PhD 2011 11
  • 12. Min. Toxic Conc. Min. Effective Conc. Previous equations suggest that we must know or determine all the parameters (i.e. AUC, 0 , K, V, F) for a given drug; therefore, it is important to know the concentration of a drug in blood (plasma or serum) and/or the amount (mass) of drug removed in urine (excretion data). Anas Bahnassi PhD 2011 12
  • 13. Onset of Action: The time at which the administered drug reaches the therapeutic range and begins to produce effect. Therapeutic Range: The plasma or serum concentration range within which the drug is likely to produce the therapeutic activity or effect Duration of Action: The time span from the beginning of the onset of action up to termination of action Termination of Action: The time at which the drug concentration in plasma falls below the minimum effective concentration Anas Bahnassi PhD 2011 13
  • 14. Amount of Drug in the Urine Anas Bahnassi PhD 2011 14
  • 15. Sites of Drug Administration 1. There is no absorption phase. Intra- 2. There is immediate Intravascular venous onset of action. 3. The entire administered Routes dose is available to Intra- produce pharmacological arterial effects. 4. This route is used more often in life-threatening situations. 5. Adverse reactions are difficult to reverse or control; accuracy in calculations and administration of drug Anas Bahnassi PhD 2011 dose, therefore, are very 15 critical.
  • 16. Sites of Drug Administration Oral Inhalation Intra- mascular Extra- vascular Sub- Rectal cutaneous Trans- Sub- dermal lingual Anas Bahnassi PhD 2011 16
  • 17. Important Features of Extravascular Routes 1. An absorption phase is present. 2. The onset of action is determined by factors such as formulation and type of dosage form, route of administration, physicochemical properties of drugs and other physiological variables. 3. The entire administered dose of a drug may not always reach the general circulation (i.e. incomplete absorption). Anas Bahnassi PhD 2011 17
  • 18. Review of the ADME Process • The process by which a drug proceeds from Absorption the site of administration to the site of measurement • the process of reversible transfer of drug to Distribution and from the site of measurement • the process of a conversion of one chemical Metabolism species to another chemical species • The irreversible loss of drug from the site of Elimination measurement. It may occur by metabolism or excretion. Anas Bahnassi PhD 2011 18
  • 19. Excretion Disposition The irreversible loss of Once a drug is in the systemic, a drug in a chemically it is distributed simultaneously unchanged or unaltered to all tissues including the organ form. responsible for its elimination. Anas Bahnassi PhD 2011 19
  • 20. Pharmacokinetic Models The change in drug’s concentration after administration can be described using certain equations mostly exponential. This suggests that ADME processes follow a first order process and therefore drug transport is mediated through passive diffusion mechanism. This means that there is a direct relationship between the plasma concentration of the drug and the amount eliminated in the urine and the original administered dose. This identifies the term Linear Pharmacokinetics. Anas Bahnassi PhD 2011 20
  • 21. Compartment Concept in PK • It is necessary to describe the pharmacokinetic parameters adequately and accurately. • The selection of the compartment model depends solely on the distribution characteristics of the drug administered. • The corresponding equation depends on the compartment model and the route of administration. Anas Bahnassi PhD 2011 21
  • 22. The model selection process is highly dependent upon the following factors. 1. The frequency at which plasma samples are collected. It is highly recommended that plasma samples are collected as early as possible, particularly for first couple of hours, following the administration of the dose of a drug. 2. The sensitivity of the procedure employed to analyze drug concentration in plasma samples. (Since inflections of the plasma concentration versus time curve in the low concentration regions may not be detected when using assays with poor sensitivity, the use of a more sensitive analytical procedure will increase the probability of choosing the correct compartment model.) 3. The physicochemical properties (e.g. the lipophilicity)of a drug. Basic Pharmacokinetics: S. Jambhekar , Phillip Breen 2009 Anas Bahnassi PhD 2011 22
  • 23. Pharmacokinetic Models Anas Bahnassi PhD 2011 23
  • 24. IV Bolus Dose - One Compartment Considering the body to behave as a single compartment. In order to simplify the mathematics it is often possible to assume that a drug given by rapid intravenous injection, a bolus, is rapidly mixed. This figure represents the uniformly mixed drug very shortly after administration. Niazi, S. 1979 Textbook of Biopharmaceutics and Clinical Pharmacokinetics, Appleton-Century-Crofts, New York, p142 Anas Bahnassi PhD 2011 24
  • 25. IV Bolus Dose - One Compartment ������ = ������0 ������ −������������ = ������������ −������������ 1 ������������������ = ������������������ − ������������ (2) E=m.lnX+b ������ − ������ ������0 − ������ = ������������ (3) ������ ������ E=E0-Rt Basic Pharmacokinetics REV. 99.4.25 3-4 1996-1999 Michael C. Makoid Niazi, S. 1979 Textbook of Biopharmaceutics and Clinical Pharmacokinetics, Appleton-Century-Crofts, New York, p142 Anas Bahnassi PhD 2011 25
  • 26. IV Bolus Two Compartment Model Often a one compartment model is not sufficient to represent the pharmacokinetics of a drug. A two compartment model often has wider application. Here we consider the body is a central compartment with rapid mixing and a peripheral compartment with slower distribution. The central compartment is uniformly mixed very shortly after drug administration, whereas it takes some time for the peripheral compartment to reach a pseudo equilibrium. Niazi, S. 1979 Textbook of Biopharmaceutics and Clinical Pharmacokinetics, Appleton-Century- Crofts, New York, p175l.;l Anas Bahnassi PhD 2011 26
  • 27. Semi-log Graph Rapid Distribution Slow Distribution Anas Bahnassi PhD 2011 27
  • 28. Absorption and Elimination One Compartment with Two Compartment with absorption phase Semi-log Graph absorption phase 28 Anas Bahnassi PhD 2011
  • 29. Anas Bahnassi PhD 2011 29
  • 30. A basic model for absorption and Disposition The model is based on mass balance considerations: At any time t, for the 1. The amount (e.g. mg) of extravascular route: unchanged drug and/or F(Dose) = absorbable amount at metabolite(s) can be measured in the absorption site + amount in the urine. body + cumulative amount 2. Drug and metabolite(s) in the metabolized + cumulative amount body (blood, plasma or serum) excreted unchanged are measured in concentration units (e.g. μgmL-1). For the intravascular route: 3. Direct measurement of drug at Dose = amount in the body + the site of administration is amount metabolized + cumulative impractical; however, it can be amount excreted unchanged: assessed indirectly. Anas Bahnassi PhD 2011 30
  • 31. Characteristics of One Compartment Model 1. Equilibrium between drug concentrations in different tissues or organs is obtained rapidly (virtually instantaneously), following drug input. Therefore, a distinction between distribution and elimination phases is not possible. 2. The amount (mass) of drug distributed in different tissues may be different. 3. Following equilibrium, changes in drug concentra- tion in blood (which can be sampled) reflect changes in concentration of drug in other tissues (which cannot be sampled). Anas Bahnassi PhD 2011 31
  • 32. Drug Concentration versus Time From a graph such as this we can see the relationship between drug concentration and drug effect. If a drug has to reach an effective concentration at a receptor site this will be reflected as a required blood concentration. Barr, W.H. 1968 Principles of Anas Bahnassi PhD 2011 32 biopharmaceutics, Amer. J. Pharm. Ed., 32, 958
  • 33. Drug Product Performance Parameters The figure shows some of the bio- pharmaceutic parameters which can be used to measure drug product performance. Later in the semester we will use the trap- ezoidal method Dittert, L.W. and DiSanto, A.R. 1973 The bioavailability of drug of calculating products, J. Amer. Pharm. Assoc., NS13, 421-432 AUC. Anas Bahnassi PhD 2011 33
  • 34. Rate Processes After administration, the drug is subject to a number of processes (ADME) whose rates control the concentration of drug in the elusive region known as ‘‘site of action.’’ These processes affect the onset of action, as well as the duration and intensity of pharmacological response. Anas Bahnassi PhD 2011 34
  • 35. Zero-order Process Applications of zero- order processes include administration of a drug as an intravenous infusion, formulation and administration of a drug through controlled release dosage forms and administration of drugs through trans-dermal drug delivery systems. Anas Bahnassi PhD 2011 35 Rectilinear Paper
  • 36. First-order Process Rectilinear Paper Anas Bahnassi PhD 2011 36
  • 37. First-order Process -dX/dt xX-1 =K, where units are mgh-1 x mg-1  K has unit is: h-1. Rectilinear Paper Anas Bahnassi PhD 2011 37
  • 38. First-order Process Rectilinear Paper Anas Bahnassi PhD 2011 38
  • 39. First-order Process Rectilinear Paper Semilogarithmic Paper Anas Bahnassi PhD 2011 39
  • 40. Comparison of Zero & First order processes Term Zero order First order -dx/dt = K0 Rate remains KX Rate changes over time constant Rate =K0 =K constant unit = mgh-1 unit=h-1 X X=X0-Kt lnX=lnX0-Kt or logX=logX0-kt/2.303 Anas Bahnassi PhD 2011 40
  • 41. Pharmacokinetics Anas Bahnassi PhD RPh abahnassi@gmail.com http://www.linkedin.com/pub/anas-bahnassi/8/707/693 http://bahnassi.coursesites.com attribution – non-commercial – share alike