1. Drug Metabolism

2. Drug Clearance through Metabolism
Drugs are eliminated from the body by:
Hepatic metabolism
Elimination in bile
Elimination in urine
Clearance (CL): amount of drug removed from body per unit time
1st order kinetics
Zero order kinetics

3. Drug Metabolism

4. Reactions of Drug Metabolism
Phase I
Phase I through P450
Specificity
Genetic variability
Inducers
Inhibitors (omeprazole, grapefruit)
Phase I not involving P450
Phase II
Reversal of Order of the Phases

5. decrease pl D conc
decrease D activity
Decrease therapeutic effect
Decrease therapeutic D effect

6. Drug Clearance by the Kidney
Glomerular filtration:
( free D cleared by ???)
Proximal tubular secretion:
(WAs & WBs)
Distal tubular reabsorption:
(lipid soluble Ds)

7. Role of Drug Metabolism

8. Clearance (continuation)
Clearance by other Routes
Total Body Clearance
Clinical Situations Resulting in Changes in t1/2

9. Design & Optimization of Dosage Regimen
Steady State Condition (Css)
Css is directly proportional to rate of
infusion
Css is inversely proportional to CL

10. Time to Reach Steady State Concentration

11. Fixed Dose / Fixed Time Interval

12. Optimization of Dose