Course Outline For Biopharmacetics and pharmacokinetics

Chapter 1 Definition and Terminology Page No

 Biopharmaceutics 1
 Drug product performance
 Biosimilarity 517
 Brand name
 Chemical Name
 Drug product selection
 Drug substance
 Generic name
 Generic substitution
 Pharmaceutical alternatives
 Pharmaceutical equivalents
 Pharmaceutical substitution
 Reference listed drugs
 Orange book
 Therapeutic alternatives
 Therapeutic substitution
 Pharmacokinetics 4
 Literal meaning and definition
 LADMER
– Liberation
– Absorption
– Distribution
– Metabolism
– Elimination
– Response
 Drug disposition
 Bioavailability 471
 Definition
 Types of Bioavailability
 Methods for measuring bioavailability
 Bioequivalence
 Pharmacodynamics

Chapter 2 Gastro-intestinal absorption 373

 Absorption (Definition and Introduction)

  Mechanism of Drug absorption
 Passive diffusion
– Carrier-mediated transport
– Active transport
 Facilitated diffusion
 Vesicular transport
 Pore transport
 Ion pair transport
 Oral drug Absorption
 Anatomical Considerations
– Oral cavity
– Esophagus
– Stomach
– Duodenum
– Jejunum
– Ileum
– Colon
– Rectum
 Physiologic Considerations
– Gastrointestinal motility
– Gastric emptying time
– Intestinal motility
– Effect of food
– Gastro-intestinal perfusion
– Effect of disease state on drug absorption

Chapter 3 Biological Half-life and Volume of distribution

1. Rate and Order of processes 40

 Zero order processes

 Definition
 Mathematical derivation
 Calculation of half life
 First Order processes
 Definition
 Mathematical derivation
 Calculation of half life
 Conversion of first order integrated rate law to
exponential rate law
 Calculation of half-life from exponential rate law
 Determination of Order
 Excercise problems (Q1-8) 43-44
 2. Volume of Distribution 267

 Definitions
 Considerations in calculations of volume of distribution.
 Case 1
 Case 2
 Case 3
 Practice problem 270

Chapter 4 Drug Clearance

 Definition 150
 Clearance models
 Physiologic Clearance model
 Non-compartmental clearance model
 Compartmental clearance model
 Relationship of clearance to elimination half-life and volume
of distribution.
 Practice problem 151
 Exercise problems (Qs 1,2,3) 171

Chapter 5 Pharmacokinetics

Application of pharmacokinetics in clinical situation 681

 Introduction
 Medication Therapy management
 Individualization of dosage regimen
 Therapeutic drug monitoring
 Drug Selection
 Dosage Regimen Design
 Pharmacokinetics of Drug
 Assay for drug
– Linearity and dynamic range
– Accuracy
– Precision
– Specificity
– Sensitivity
– Stability
– Ruggedness
 Pharmacokinetic evaluation
 Dosage readjustment
 Monitoring serum concentration
  Design of Dosage Regimen
 Individualized Dosage Regimen
 Dosage regimen based on population averages
 Dosage regimen based on partial pharmacokinetic
parameters
 Nomograms and tabulation in dosage regime designs
 Empirical dosage regimen
 Conversion Of IV to Oral dosing
 Practice problems 695
 Determination of Dose
 Practice problems 696
 Determination of Dose and dosing interval
 Practice problems 699
 Dosing Infants and children
 Practice problems 702
 Dosing the elderly
 Practice problems 703
 Dosing the obese patients
 Practice problems 706
P.S: the practice problems are Qs: 1, 2, 3, 4, 5, 6, 10, 11, 12, 13) 725-727

 Pharmacokinetics of drug interaction Slides

 Definition
 Epidemiology
 Risk factors
 Outcomes of drug interactions
 Mechanisms of drug interactions
– Pharmacokinetic interactions
1. Absorption interaction
2. Distribution interaction
3. Metabolism interaction
4. Excretion interactions
– Pharmacodynamics interactions
1. Agonistic effect
2. Antagonistic effect
3. Alteration at receptor site
4. Alter electrolyte concentration
 Types of drug interactions
– Drug-drug interactions
– Drug-food interactions
– Drug-excipient interactions
1. Physical interactions
2. Chemical interactions
3. Biopharmaceutical-interactions
 4. Excipient-excipient interactions
– Drug-Condition/diseases interactions
 Reducing risk of interactions
 Role of pharmacist in avoiding drug interactions
 Population Pharmacokinetics
 Difference between individual and population
pharmacokinetics
 Difference between geographical and regional
pharmacokinetics

Chapter 6 Bioavailability and Bioequivalence 469

1. Bioavailability
 Definition
 Importance
 Pharmacokinetic Parameters
 Types of Bioavailability
 Relative bioavailability
 Absolute bioavailability
 Bioavailability requirements

2. Bioequivalence
 Definition
 Bioequivalence criteria
 Bioequivalence requirements
 Biowaivers

3. Methods for assessing BA and BE

 Plasma drug concentration
 Urinary drug excretion
 In vivo pharmacodynamics (PD) comparison
 Clinical endpoint study
 In vitro studies

4. BA and BE studies and protocols

 Selection of drug product, volunteer/subject, study design
 Study Components
 Clinical
I. Good clinical practice (GCP)
II. Independent ethics committee (IEC)
III. Written Informed consent
 IV. Institutional Review board (IRB)
V. Quality Assurance (QA)
VI. Quality control (QC)
VII. Dosing details and compliance
VIII. Drug acquisition, labeling, packaging and storage
IX. Study subjects
 Analytical
I. Specificity
II. Sensitivity
III. Linearity and dynamic change
IV. Precision
V. Accuracy
VI. Stability
VII. Ruggedness
 Data Analysis
 Statistical interpretation
(for both data analysis and statistical
interpretation)
I. Pharmacokinetic evaluation
II. Data package for determination of plasma drug
concentration
III. SPSS
IV. MS Excel program

 Study design
 Cross over study design
 Parallel Study design
 Blind study

 BE study designs
 Fasting study
 Food intervention study
 Multi-dose study design

Chapter 7 Concept of Compartment models

 Model 15-20
 Modeling
 Compartments
 Pharmacokinetic models
 Compartmental models
– Mammillary model
I. One compartmental model
II. Two compartmental model
 III. Multicompartmental model
– Catenary model
 Non-compartmental model
 Physiological model
 Difference between open pk model and closed pk model
One compartment model 75
 Definition of one compartment model
 Assumptions
 Graphic model (figure)
 Equation
 Graphs
 Parameters
 Elimination rate constant
 Elimination Half-life
 Volume of distribution
 Clearance
 AUC
 Practice problems 87,88,90-
92
Two compartment model 100
 Definition of model
 Assumptions
 Graphic model (figures)
 Method of residuals
 Equation
 Graph
 Parameters
 Elimination rate constant
 Clearance
 Volume of distribution
– Apparent volume of distribution at steady state
– Volume of central compartment
– Extrapolated volume of distribution
– Volume of distribution by area
Three Compartment model______________________________
 Definition of model
 Assumptions
 Method of residual (definition and types)
 Graphic model (figures)
 Equation
 Graph
 Parameters
 Half life
  Apparent volume of distribution
 Elimination rate constant
 Area under curve
 Practice problems 107,110,
113,
 Exercise problems 124(all
qs)
P.S: All derivation of formulas are included

Chapter 8 Multiple dosage regimens

 Introduction PL
 Intravenous Administration Madan
– Drug accumulation
1. During first dose
2. During second dose
3. During third dose
– Persistence factor
– Loss factor
– Accumulation factor
 Mathematical treatment
– Cmax ss and Cmin ss of First dose
– Cmax ss and Cmin ss of Second dose
– Cmax ss and Cmin ss of Third dose
– Cmax ss and Cmin ss of Fourth dose
– General equations
1. Maximum plasma concentration
2. Minimum plasma concentration
 Steady state concentrations
– Relationship between Cmax ss and Cmin ss
 Factors influencing steady dose concentrations
– Effect of dose
– Effect of dosing interval
 Extravascular Administration
– Steady state concentrations
1. Cmax ss
2. Cmin ss
3. Relationship between Cmax ss and Cmin ss
– Factors influencing steady state concentrations
1. Effect of dose
2. Effect of dosing interval
  Practice problems (all examples and exercise questions
are included)

Chapter 9 Elimination of drugs

 Introduction
 Biotransformation
 Excretion
Hepatic Drug Elimination 309
 Introduction
 Enzyme kinetics
 Michaelis-Menten equation
 Kinetics of enzyme inhibition
 Drug biotransformation reactions
 Introduction
 Drug metabolites
 Classification of biotransformation
 Pathways of drug biotransformation
– Phase I reactions
– Phase II reactions
 Hepatic enzymes in biotransformation
 Mixed function oxidases
 Phase II enzymes
 Thiopurine S-methyltransferase
 Uridine diphosphate (UDP) glucoronosyltransferase
 N-acetyl transferase
 First pass effect
 Definition
 Evidence of first pass effect
– Absolute Bioavailability
– Liver extraction ratio
– Relationship between absolute bioavailability and
liver extraction ratio
 Hepatic clearance of a protein bound drugs
 Biliary excretion of drugs
 Composition of bile
 Drugs excreted in bile
 Elimination of biliary clearance
 Entero-hepatic circulation
 Significance of biliary excretion
Renal Excretion of drugs 149
 Renal Drug Elimination
 Glomerular Filtration
 – Measurement of GFR
– Criteria for markers
I. Inulin
II. Blood Urea Nitrogen
III. Creatinine
– Serum creatinine concentration and creatinine
clearance
– Calculation of creatinine clearance from serum
creatinine concentration
 Active tubular secretion
 Tubular Reabsorption
 Renal Clearance
Other Routes
 Pulmonary excretion
 Salivary excretion
 Mammary excretion
 Skin excretion
 Genital excretion

Chapter 10 Protein binding 273

 Definition
 Types of drug protein binding
 Irreversible drug protein binding
 reversible drug protein binding
 Methods to study drug protein binding
 Plasma proteins
 Albumin
 Alpha-1 acid glycoprotein
 Immunoglobins
 Lipoproteins
 Erythrocytes
 Determinants of protein binding
 The drug
 The protein
 The affinity between drug and protein
 Drug interactions
 The pathophysiologic condition of the patient
 Kinetics of protein binding
 Clinical Significance of drug-protein binding
 Drug distribution and pharmacodynamics
Chapter 11 Pharmacokinetic variations in disease states
 Pharmacokinetic considerations 775
 General approaches for dose adjustments in renal diseases 777
 Dose adjustment based on drug clearance
 Dose adjustments based on changes in elimination rate
constant
 Dose adjustments for uremic patients 785
 Fractions of drug excreted unchanged methods 787
 Practice problems 787,
792,
793
Chapter 12 Pharmacokinetics of IV infusion 131
 Introduction
 Advantages
 One compartment model drugs
 Steady state concentration and time needed to reach Css
 Infusion method for calculating patient elimination half life
 Loading dose plus IV infusion one compartment models
 Estimation of drug clearance and Vd from infusion data
 Practice problem (all practice problems are included)
 Exercise problems (qs 1-7) 144-145

Chapter 13 Biopharmaceutical aspects in developing a dosage form

 Biopharmaceutic Considerations 418-423

 Biopharmaceutics Classification system
 Rate limiting steps in drug absorption
 Disintegration
 Dissolution and solubility
 Pharmacodynamic considerations
 Therapeutic objectives
 Toxic effects
 Adverse effects
 Drug considerations Pg 73-74
 Physicochemical properties for consideration in drug (CPR)*
product design
– Drug solubility and dissolution
– Particle size and surface area
– Partition co-efficient and extent of ionization
– Salt formation
– Polymorphism
– Chirality
– Hydrates and complexes
 – Complex formation
 Drug product consideration
 Pharmacokinetic considerations
 Bioavailability of drug
 Route of administration
 Desired dosage form
 Desired dose
 Patient Consideration
 Compliance and acceptability of drug product
 Cost of dosage form
 Manufacturing considerations
 Availability of raw material
 Stability
 Method of manufacture
 Cost of quality
 Process validation
 Quality control
 Quality assurance

Chapter 14 In-vitro and In-vivo correlation (IVIVC) 438

 In-vitro methods
 In-vivo methods
 In-vitro in-vivo correlation
 Roles of IVIVC
 Need of IVIVC
 In-vivo methods
 In-vivo variables used in IVIVC
– Plasma Drug Concentration
– Urinary Drug excretion data
– Acute pharmacodynamics effect
– Clinical observations
 In-vitro studies
 Relationships made in IVIVC
– Dissolution rate vs. Absorption rate
– Percent of drug dissolved vs. percent of drug
absorbed
– Maximum plasma concentration vs. percent of
drug dissolved in-vitro
– Serum drug concentration vs. percent of drug
dissolved
 Levels of correlation
– Level A correlation
– Level B correlation
 – Level C correlation
– Level D correlation
 Biopharmaceutics Classification and BCS:
 Applications of IVIVC