Anaes · Applied cardiovascular & respiratory physiology

Pharmacokinetics: compartment models

Also known as Pharmacokinetics · Compartment model · Volume of distribution · Clearance · Half-life · Redistribution

Pharmacokinetics describes what the body does to the drug — absorption, distribution, metabolism and excretion — and the compartment model is the mathematical framework that predicts drug concentration over time. The framework rests on five exam-critical ideas: the body is modelled as connected compartments (the central compartment of plasma and well-perfused tissues, a fast peripheral compartment of muscle, and a slow peripheral compartment of fat) between which the drug distributes and redistributes; the volume of distribution (Vd) is the apparent volume that would contain the total drug at the plasma concentration — a large Vd means the drug has left the plasma for the tissues (lipophilic drugs); clearance (CL) is the volume of plasma cleared of drug per unit time, and is the main determinant of the maintenance infusion rate; the elimination half-life (t1/2) is the time for the plasma concentration to fall by 50 percent, determined by Vd and CL (t1/2 equals 0.693 times Vd over CL); and redistribution from the peripheral compartments back to the central compartment is the mechanism by which a single IV bolus of thiopental or propofol wears off — the drug has not been metabolised, it has redistributed to muscle and fat, dropping the brain concentration below the effect threshold. Built on the obese-cardiac Marsh-vs-Schnider induction study (Ye 2026, n-118, 59 per arm, Marsh total-weight vs Schnider lean-weight, delta-C NS during TCI with Marsh lower after cessation p less than 0.05, higher BIS with preserved LVEF/SV and shorter recovery), the four-model propofol LOC comparison (Introna 2026, retrospective neurosurgical, Ce at LOC about 1.5 Marsh/Eleveld to 4.6 Schnider mcg/mL, model effect p less than 0.001, brain lower than spine), the paediatric IV melatonin PK study (Garioud 2026, n-20 age 1 to 6, 0.15 mg/kg, Cmax 416298, t-half 35.2 min, CL 0.0183, Vd 0.92), the remimazolam narrative review (Dong 2025, esterase to inactive CNS7054, high clearance with small Vss and short half-life without accumulation, flumazenil reversal), the LC-MS/MS propofol assay study (Ng 2026, 25 to 5000 ng/mL, 92 percent recovery, single-patient 648 to 4356 ng/mL application), and the propranolol virtual trial (Marques 2026, n-125 simulated, two-compartment, health-to-clearance with BSA-to-central-volume, renal impairment worsens omeprazole interaction, below toxicity, not directly clinical). Compartment equations, half-life arithmetic, and CSHT minute-values below are viva teaching carried with honesty notes, not numbers from these abstracts.