Biopharmaceutics and Pharmacokinetics
This domain tests ADME, bioavailability, first-pass metabolism, compartmental thinking and the equations used to individualise a dose. Expect calculation items with a clinical wrapper.
Core parameters and equations
Bioavailability (F), Cmax, Tmax, AUC, volume of distribution (Vd), clearance (CL), half-life and fraction unbound. The working relationships: CL = k × Vd; t½ = 0.693 × Vd / CL; loading dose = (Vd × target concentration) / F; maintenance rate = (CL × target concentration) / F; AUC = F × dose / CL. Steady state is reached in about four to five half-lives.
Kinetic behaviour
Most drugs follow first-order (linear) kinetics, so concentration rises proportionally with dose. Phenytoin, ethanol and high-dose salicylates saturate and follow Michaelis–Menten kinetics: small dose increases produce large, unpredictable concentration jumps. First-pass metabolism lowers oral bioavailability; enterohepatic recycling prolongs half-life.
Worked example
A drug has Vd = 50 L and CL = 5 L/h in a 70 kg patient. Half-life = 0.693 × 50 / 5 = 6.93 h, about 7 h, so steady state takes roughly 28–35 h. For a target steady-state concentration of 2 mg/L with F = 1, maintenance rate = 5 × 2 = 10 mg/h, i.e. 240 mg per day. If the same drug were given orally with F = 0.5, the daily oral dose would double to 480 mg.
Traps
- Confusing half-life with duration of effect; a half-life predicts accumulation, not efficacy.
- Using total body weight for hydrophilic drugs in obesity, or ignoring adjusted weight for aminoglycosides.
- Applying linear-dose arithmetic to phenytoin.
- Forgetting to divide by F when converting an intravenous dose to an oral one.