Drug Metabolism.

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Presentation transcript:

Drug Metabolism

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

Drug Metabolism

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

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

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

Role of Drug Metabolism

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

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

Time to Reach Steady State Concentration

Fixed Dose / Fixed Time Interval

Optimization of Dose