PH1.6 | PH1.6 | Pharmacokinetics Across ADME — SDL Guide — Summary & Reflection

KEY TAKEAWAYS

Pharmacokinetics (ADME) is the quantitative description of how a drug moves through the body:

Absorption: governed by passive diffusion of the non-ionised, lipophilic drug form (pH-partition theory); bioavailability (F) is reduced by incomplete absorption and first-pass hepatic metabolism; IV = 100% bioavailability by definition.

Distribution: determined by plasma protein binding (only free drug is active and distributable), volume of distribution (Vd = Dose / initial C — NOT a real volume; high Vd = extensive tissue binding), and physiological barriers (BBB requires lipophilic drugs; placenta is permeable to most drugs).

Metabolism: Phase I (CYP450 — oxidation, reduction, hydrolysis; produces active or inactive or toxic metabolites; prodrugs activated here) then Phase II (conjugation — glucuronidation, sulfation, etc.; produces water-soluble inactive conjugates). Enzyme induction (rifampicin) decreases drug levels; enzyme inhibition (erythromycin, fluconazole) increases drug levels.

Excretion: primarily renal (GFR + tubular secretion − tubular reabsorption); pH manipulation affects ionisation and reabsorption; biliary excretion + enterohepatic recirculation prolongs t½.

Key parameters: t½ = 0.693 × Vd / CL; steady state reached after 4–5 t½ (independent of dose); loading dose = Vd × target Css / F; first-order kinetics (constant fraction) vs zero-order kinetics (constant amount — phenytoin, ethanol — dangerous dose-concentration non-linearity).

REFLECT

Think about a drug you have encountered in a clinical or ward setting where the dose was adjusted for renal impairment, hepatic disease, or extreme body weight. Which ADME parameter was being modified by that adjustment? What would have happened if the adjustment had not been made? Write two or three sentences explaining the PK reasoning behind that dose modification using the concepts from this SDL.