Pharmacokinetics
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Direct answer
Pharmacokinetics is what the body does to a drug — its absorption, distribution, metabolism and excretion (ADME) — quantified by bioavailability, volume of distribution, clearance and half-life. Pharmacodynamics, its counterpart, is what the drug does to the body; together they set the dose, the interval and the route. Kinetic parameters dominate theory papers and bedside prescribing.
What you must remember
- Bioavailability is the fraction of an administered dose reaching the systemic circulation unchanged — complete intravenously; first-pass presystemic metabolism by gut wall and liver reduces it, classically for glyceryl trinitrate, propranolol and morphine.
- Volume of distribution (Vd) equals the amount of drug in the body divided by plasma concentration; a large Vd implies tissue sequestration (amiodarone, chloroquine, digoxin), and only the unbound fraction of plasma protein-bound drug is active and filterable.
- Metabolism: phase I reactions (mainly CYP450 oxidation) and phase II conjugations (glucuronidation, sulphation, acetylation) mostly inactivate drugs; enzyme inducers — phenytoin, carbamazepine, rifampicin, phenobarbitone, chronic alcohol; inhibitors — cimetidine, ciprofloxacin, erythromycin, ketoconazole, grapefruit juice.
- Excretion is chiefly renal — filtration, active tubular secretion (probenecid blocks penicillin secretion) and pH-dependent reabsorption — plus biliary excretion with enterohepatic recycling.
- Half-life equals 0.693 times Vd divided by clearance; it sets the dosing interval, and steady state is reached after four to five half-lives of regular dosing.
- Most drugs follow first-order kinetics (a constant fraction eliminated per unit time), but ethanol, phenytoin and high-dose salicylates saturate elimination and follow zero-order kinetics — a constant amount removed, so small dose rises cause large plasma jumps.
- The loading dose fills the volume of distribution at once; the maintenance dose simply replaces what clearance removes each interval; therapeutic drug monitoring guides digoxin, phenytoin, lithium, theophylline and aminoglycosides.
Common confusion
First-order and zero-order kinetics are endlessly swapped. In first-order kinetics a constant fraction is eliminated and half-life is fixed; in zero-order kinetics enzymes are saturated, half-life varies with concentration, and the dose-plasma level curve climbs steeply — phenytoin toxicity after a small dose increment is the classic example. Loading and maintenance doses are a second trap: loading fills the volume of distribution quickly; maintenance merely replaces daily losses.
Exam-focused takeaway
Theory answers should define each ADME phase and parameter, give the half-life formula, and contrast first with zero-order kinetics with named drugs. Viva examiners ask for first-pass effect examples, consequences of enzyme induction and when to use a loading dose. MCQs test bioavailability of one for intravenous routes, steady state at four to five half-lives, the zero-order drug list, and volume of distribution or half-life calculations.
Frequently asked questions
What is bioavailability?
The fraction of the administered dose reaching the systemic circulation unchanged; one hundred per cent intravenously, and reduced orally by incomplete absorption and first-pass metabolism.
When is steady state achieved?
After about four to five half-lives of repeated dosing, when the amount administered per dose equals the amount eliminated per dosing interval.
Which drugs show zero-order kinetics?
Ethanol, phenytoin and salicylates at high doses — their elimination saturates, so removal occurs at a constant amount per unit time.
Why does plasma protein binding matter clinically?
Only unbound drug acts, crosses membranes and is filtered; displacement, as with warfarin or phenytoin, raises free levels and toxicity risk.
Why is a loading dose given?
To fill the volume of distribution rapidly and reach the target concentration at once rather than waiting four to five half-lives — vital for digoxin or phenytoin when urgency matters.