Pharmacokinetics, Biopharmaceutics, and Therapeutic Drug Monitoring
What the domain tests
This domain tests quantitative drug disposition: absorption, bioavailability, volume of distribution, clearance, half-life, loading and maintenance dosing, and TDM interpretation. Israeli exam questions often require a calculation plus an interpretation of a drug level in a specific clinical context.
Core rules and concepts
- Clearance determines maintenance dose rate; volume of distribution determines loading dose. Half-life is proportional to Vd and inversely proportional to clearance.
- Loading dose = (Vd × target concentration)/bioavailability. Maintenance dose rate = clearance × target concentration/bioavailability.
- For TDM, interpret levels with sampling time, steady-state status, protein binding, and interacting drugs. Vancomycin troughs, aminoglycoside peaks/troughs, digoxin, lithium, phenytoin, and theophylline are common.
- Bioavailability (F) is the fraction reaching systemic circulation; first-pass metabolism reduces oral F. Food, formulation, and transporters alter absorption.
- In obesity, use adjusted body weight for some drugs; in renal impairment, estimate creatinine clearance and adjust renally cleared drugs.
Worked example
A 70 kg patient needs a theophylline loading dose to reach 10 mg/L. Assume Vd = 0.5 L/kg and F = 1. Vd = 35 L. Loading dose = 35 L × 10 mg/L = 350 mg. The reasoning: loading dose fills the apparent distribution volume, not the maintenance requirement. If the patient is obese or has altered Vd, the estimate changes. A maintenance dose would instead use clearance and would be calculated after steady state is considered.
Traps that cost marks
Do not draw a level before steady state unless a loading dose was given and the timing is appropriate. Do not interpret a trough as a peak. Do not use total body weight automatically in obesity. Do not forget that hypoalbuminemia changes free phenytoin and interpretation of total drug levels.
Key points
- Loading dose uses Vd; maintenance dose uses clearance.
- Half-life = 0.693 × Vd/CL.
- TDM interpretation requires timing and clinical context.
- First-pass metabolism lowers oral bioavailability.
- Renal function must guide dose adjustment.