Lecture 2

1. Factors affecting the concentration of drugs in body

i. Volume of Distribution (Distribution of drug across body)
 Total amount of drug in body / Plasma concentration of drug
ii. Clearance (Rate of drug is removed from body)
 Rate of elimination / Plasma concentration of drug
 Factor affecting clearance
A. Age
B. Disease
Rate of elimination
 Clearance x Plasma concentration of drug
 Factor affecting rate of elimination
A. Concentration of drug in blood (Capacity-Limited Elimination)
B. Rate of Blood flow (Flow-Dependent Elimination)

2. Half life

3. Bioavailability (Rate and extent to which drug reaches the systemic circulation)
 AUC of a particular route of administration / AUV by IV administration
 Factor affecting bioavailability
A. First-pass hepatic metabolism
B. Solubility of drug (lipid solubility & water solubility)
C. Chemical instability (pH, enzyme)
D. Nature of drug formulation (size, salt form, coating)

4. 4 Phases of pharmacokinetic (ADME)

i. Absorption (Process that drug passes through barriers before entering the bloodstream)
 Drug move in 2 ways: Bulk flow & Diffusion
 4 ways for small molecule cross cell membranes
 Factor affecting membrane permeation of drugs by simple diffusion
A. pH (pH of drug affect ionisation of drug in a particular pH environment)
B. Ionisation (Ionised -> Charged -> Low lipid solubility -> Low membrane permeation)
A+B = Ion trapping
ii. Distribution
 Rate of blood flow
 Protein binding
 Partition into body fat
iii. Metabolism (Anabolism & Catabolism)
Phase 1 reaction: Introducing a restive group by adding one atom of oxygen by CYP450 system
Phase 2 reaction: Conjugation -> Inactive production (Detoxification)
iv. Excretion
Renal excretion
Biliary excretion (Secrete to small intestine)