Unit 1346: Pharmacokinetics

1. Introduction to Pharmacokinetics

• Definition of pharmacokinetics
• Importance in pharmacology and drug therapy
• Overview of key pharmacokinetic processes: Absorption, Distribution, Metabolism, Elimination (ADME)

2. Absorption of Drugs

2.1. Mechanisms of Absorption

• Passive diffusion
• Facilitated diffusion
• Active transport
• Endocytosis

2.2. Routes of Administration

• Oral
• Intravenous
• Intramuscular
• Subcutaneous
• Inhalation
• Topical

2.3. Factors Influencing Drug Absorption

• Physicochemical properties of drugs (solubility, ionization, molecular size)
• Formulation and dosage form
• Gastrointestinal pH and motility
• Presence of food or other drugs

3. Distribution of Drugs

3.1. Principles of Drug Distribution

• Role of blood circulation
• Tissue permeability
• Plasma protein binding

3.2. Factors Affecting Distribution

• Lipid solubility
• Blood flow to tissues
• Barriers (e.g., blood-brain barrier, placental barrier)
• Volume of distribution concept

4. Metabolism (Biotransformation) of Drugs

4.1. Overview of Drug Metabolism

• Purpose and importance
• Phase I reactions: oxidation, reduction, hydrolysis
• Phase II reactions: conjugation (glucuronidation, sulfation, acetylation)

4.2. Role of the Liver

• Cytochrome P450 enzyme system
• Factors that influence metabolism (genetics, age, disease, induction, inhibition)

4.3. Implications of Metabolism

• Impact on drug activity (activation, inactivation)
• Toxic metabolites

5. Elimination of Drugs

5.1. Routes of Elimination

• Renal excretion (glomerular filtration, tubular secretion, reabsorption)
• Hepatic elimination and biliary excretion
• Other routes (lungs, sweat, saliva)

5.2. Factors Affecting Elimination

• Renal and hepatic function
• Drug properties

6. Pharmacokinetic Parameters

6.1. Half-life (t½)

• Definition and significance
• Calculation and interpretation

6.2. Clearance (Cl)

• Definition and types (renal, hepatic, total)
• Calculation

6.3. Volume of Distribution (Vd)

• Concept and clinical relevance

6.4. Bioavailability (F)

• Definition
• Factors influencing bioavailability

6.5. Other parameters

• Area under the curve (AUC)
• Peak concentration (Cmax)
• Time to peak concentration (Tmax)

7. Pharmacokinetics of Special Populations

7.1. Pediatric Patients

• Differences in absorption, distribution, metabolism, elimination
• Dose adjustments

7.2. Geriatric Patients

• Age-related pharmacokinetic changes
• Polypharmacy considerations

7.3. Pregnant Patients

• Physiological changes affecting pharmacokinetics
• Placental drug transfer

7.4. Patients with Renal or Hepatic Impairment

• Impact on drug clearance
• Dose modifications

8. Pharmacokinetic Drug Interactions

8.1. Absorption Interactions

• Altered gastric pH
• Complex formation

8.2. Metabolic Interactions

• Enzyme induction and inhibition
• Impact on drug levels and toxicity

8.3. Distribution and Elimination Interactions

• Displacement from plasma proteins
• Competition for excretion pathways

9. Pharmacokinetic Modeling and Simulation

9.1. Mathematical Models

• Compartmental models (one-compartment, two-compartment)
• Non-compartmental analysis

9.2. Simulation Tools

• Use in dose optimization
• Predicting drug concentrations over time

9.3. Applications in Drug Development and Clinical Practice

10. Clinical Application of Pharmacokinetics

10.1. Personalized Medicine

• Individualizing drug doses based on pharmacokinetics

10.2. Therapeutic Drug Monitoring (TDM)

• Rationale and methods

10.3. Improving Drug Safety and Efficacy

• Dose adjustments in special populations
• Managing drug interactions

Summary and Integration

• Recap of ADME and pharmacokinetic principles
• Case studies illustrating clinical application