Pharmacokinetics basics
ADME, half-life, bioavailability, volume of distribution, and clearance — explained for anyone who wants to understand why drugs are dosed the way they are.
What is pharmacokinetics?
Pharmacokinetics is the study of how the body processes a drug over time — how it gets in, where it goes, how it is broken down, and how it leaves. The name comes from the Greek pharmakon (drug) + kinesis (movement).
PK is distinguished from pharmacodynamics (PD), which studies what the drug does to the body. Together, PK and PD explain why two patients taking the same dose may have different responses — their bodies process the drug differently.
Comprehensive PK reference texts include the NCBI StatPearls pharmacokinetics chapter and EMA clinical pharmacology guidelines.
ADME: the four processes
How drug enters the bloodstream from its site of administration. Oral drugs dissolve in the GI tract and cross the intestinal wall. Affected by solubility, particle size, GI motility, and efflux transporters (e.g., P-gp). Quantified by bioavailability (F).
How drug spreads from blood into tissues. Driven by lipophilicity, plasma protein binding, and tissue perfusion. Quantified by volume of distribution (Vd).
Chemical transformation — mostly in the liver by CYP enzymes. Creates metabolites that may be active or inactive. First-pass metabolism can substantially reduce oral bioavailability before drug reaches systemic circulation.
Removal of drug from the body — via kidney (renal) or bile (biliary/faecal). Quantified by clearance (CL) and half-life (t½). Renal/hepatic impairment slows elimination and requires dose adjustments.
Key pharmacokinetic parameters
| Parameter | Symbol | Definition | Units |
|---|---|---|---|
| Bioavailability | F | Fraction of dose reaching systemic circulation | 0–1 (or %) |
| Half-life | t½ | Time for plasma concentration to fall by 50% | h, min, days |
| Volume of distribution | Vd | Apparent volume in which drug is dissolved | L or L/kg |
| Clearance | CL | Volume of plasma cleared of drug per unit time | L/h or mL/min |
| Peak concentration | Cmax | Maximum plasma concentration after a dose | mg/L, ng/mL |
| Time to peak | Tmax | Time after dosing at which Cmax is reached | h, min |
| Area under curve | AUC | Total drug exposure over time; proportional to dose/CL | mg·h/L |
| Protein binding | %PB | Fraction of drug bound to plasma proteins (albumin, AAG) | % |
Reference: FDA Non-Compartmental Analysis guidance and NCBI StatPearls PK chapter.
The one-compartment model
The simplest PK model treats the body as a single well-mixed compartment. After an intravenous bolus, plasma concentration decays exponentially:
For oral dosing, absorption and elimination compete, producing a characteristic rise-then-fall curve:
This is the model behind the ibuprofen dose-curve simulator on the drug page. The NCBI PK chapter covers two-compartment and non-linear (Michaelis-Menten) extensions.
Special populations
PK parameters vary with age, organ function, genetics, and body composition. Drug labels must include dosing guidance for populations where differences are clinically meaningful.
Reduced GFR slows elimination of renally cleared drugs. Dose reduce or extend interval. GFR estimated via CKD-EPI equation.
Reduced CYP enzyme activity and albumin synthesis alter metabolism and protein binding. Child-Pugh or MELD score guides dosing. See FDA hepatic impairment guidance.
Neonates have immature CYP enzymes and higher Vd (more body water). Dose is weight-based. FDA's paediatric drug development resources cover PREA requirements.
CYP2D6 and CYP2C19 genetic variants create poor/rapid metaboliser phenotypes. FDA's pharmacogenomic biomarker table lists drugs with genotyping implications.