Basic pharmaceutical sciences: formulation, medicinal chemistry and pharmacokinetics
Core sciences that drive dosing
Basic pharmaceutical sciences connect formulation, molecular structure and kinetics. In pharmaceutics, know how dosage form, particle size, salt form, excipients and manufacturing affect dissolution, absorption and stability. Bioavailability (F) is the fraction of dose reaching systemic circulation unchanged; it incorporates absorption and first-pass metabolism. For medicinal chemistry, focus on ionisation and pKa, lipophilicity, protein binding, chiral centres, prodrugs and functional groups that alter receptor binding or stability. A charged drug at physiological pH often has low passive membrane permeability; a prodrug is inactive until biotransformation.
In pharmacokinetics, distinguish volume of distribution (Vd), clearance (CL), half-life (t1/2) and bioavailability. Vd is an apparent volume, not a real anatomical space; it relates amount in body to plasma concentration. CL is the volume of plasma cleared per unit time and is additive across organs. For linear (first-order) kinetics, t1/2 ≈ 0.693 × Vd/CL. Steady state is reached after about 4–5 half-lives; accumulation depends on dosing interval and t1/2. Zero-order elimination occurs when clearance pathways saturate, so concentration rises disproportionately with dose.
Traps: confusing half-life with duration of effect; assuming a large Vd means drug is in plasma; forgetting that loading dose depends on Vd while maintenance dose depends on CL; ignoring protein binding when interpreting total drug concentration; and mixing up potency with pharmacokinetic exposure.
Worked rule: loading dose = (Vd × target concentration)/F; maintenance rate = (CL × target concentration)/F. Check units and whether F is a fraction. If F is unknown, state assumptions rather than inventing a value.