Clinical Pharmacokinetics and Pharmacodynamics
What the exam tests
Clinical pharmacokinetics and pharmacodynamics questions ask you to turn a patient's physiology into a dose, then justify it with equations and target concentrations. Expect calculations, TDM interpretation, and dosing in renal or hepatic impairment.
Core relationships
- Clearance (CL) = dose/AUC; at steady state CL = (F × dose)/(Css × τ).
- Volume of distribution (Vd) = amount in body/plasma concentration; loading dose = (Vd × target C)/F.
- Half-life = 0.693 × Vd/CL; steady state is reached after about 4–5 half-lives.
- For time-dependent killers, target fT>MIC; for concentration-dependent killers, target Cmax/MIC or AUC/MIC.
- Estimate creatinine clearance with Cockcroft–Gault; choose ideal body weight in obesity and adjust for amputation.
Monitoring
Vancomycin: AUC24/MIC 400–600 for MRSA; trough-only monitoring is inferior. Aminoglycosides: extended-interval dosing with a single level and nomogram. Phenytoin: correct the measured level for hypoalbuminemia; free phenytoin is about 10% of total. Digoxin: sample at least 6–8 hours post-dose; toxicity risk rises with hypokalemia, hypomagnesemia and renal failure. Lithium has a narrow window and is renally cleared.
Worked example
A 70-year-old, 60 kg woman with CrCl 35 mL/min needs IV vancomycin. A loading dose of 25 mg/kg (1,500 mg) is reasonable, then maintenance based on AUC. Because vancomycin is 50% protein bound and largely renally cleared, reduce the daily dose and monitor a trough before the fourth dose and an AUC if available. Target AUC24 400–600 mg·h/L, not a random peak.
Traps
Mixing total and free concentrations; using actual body weight in obesity for aminoglycosides; forgetting salt conversion (phenytoin sodium contains about 92% phenytoin base); interpreting a level drawn at the wrong time; assuming a long half-life always means a large Vd.