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Drug Metabolism

Drug Metabolism. Drug Clearance through Metabolism. Zero order kinetics. 1 st order kinetics. 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. Drug Metabolism.

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Drug Metabolism

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  1. Drug Metabolism

  2. Drug Clearance through Metabolism Zero order kinetics 1st order kinetics • 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

  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 t1/2

  11. Fixed Dose / Fixed Time Interval

  12. Optimization of Dose

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