Pharmaceutical Sciences: Pharmaceutics, Pharmacology, Medicinal Chemistry and Pharmacokinetics
What this domain tests
Pharmaceutics, pharmacology, medicinal chemistry and pharmacokinetics are tested as an integrated set: how formulation affects absorption, how structure affects receptor binding, and how ADME determines dose and interval. Expect bioavailability, first-pass metabolism, volume of distribution, clearance, half-life, zero- versus first-order kinetics, CYP induction/inhibition, protein binding, prodrugs, stereochemistry and BCS classification.
Core rules
- Bioavailability (F) is the fraction of an extravascular dose reaching systemic circulation unchanged; it is not the same as absorption rate.
- Volume of distribution Vd = amount in body / plasma concentration; it reflects tissue binding, not a real anatomical space.
- Clearance CL is the volume of plasma cleared per unit time; at steady state, maintenance rate = CL × target concentration (for a drug with linear kinetics).
- Half-life t½ = 0.693 × Vd / CL; it changes if either Vd or CL changes.
- Loading dose = (Vd × target concentration) / F; it depends on Vd and F, not on CL.
- First-order elimination: constant fraction per unit time. Zero-order: constant amount per unit time (e.g., phenytoin at high concentrations, ethanol).
- CYP3A4 is a major source of interactions; inhibition raises substrate levels quickly, induction develops over days to weeks.
Worked example
A drug has F = 0.5, CL = 10 L/h, Vd = 100 L, and a target steady-state concentration of 2 mg/L. The half-life is 0.693 × 100 / 10 = 6.93 h. The maintenance rate is CL × Css = 10 L/h × 2 mg/L = 20 mg/h, which is 480 mg/day. Because F is 0.5, the oral maintenance dose must be doubled: 40 mg/h, or 960 mg/day. The loading dose is (100 L × 2 mg/L) / 0.5 = 400 mg. If the patient develops renal failure and CL falls, the maintenance dose falls but the loading dose is unchanged.
Traps
Do not use total drug concentration when interpreting a highly protein-bound drug with a narrow therapeutic index; do not confuse half-life with duration of action; do not assume a larger Vd means faster elimination; do not forget that prodrugs require activation (e.g., clopidogrel via CYP2C19); do not apply first-order formulas to zero-order drugs.