Past Papers · SAQ
Multi-compartment Pharmacokinetics
2026A Q19
Exam questiona) Explain the multi-compartment pharmacokinetic model (80% of marks). b) Outline with examples, the characteristics of drugs that adhere to this model (20% of marks).
CICMWrecks answer
Master answer
a) Multi-compartment pharmacokinetic model (80%)
Concept: the body is represented as a series of kinetically distinct compartments rather than one homogeneous volume. Drug concentration is usually measured in the central compartment, while drug simultaneously distributes to and from one or more peripheral compartments.
Compartments
| Compartment | Typical contents | Role |
|---|---|---|
| Central (V1) | Plasma and rapidly equilibrating, highly perfused tissues | Initial drug distribution and usual site of plasma concentration measurement; elimination commonly occurs from here. |
| Peripheral (V2, V3…) | Progressively slower-equilibrating tissues | Receive drug from the central compartment and later return drug to it. |
After an IV bolus
- Early rapid fall in plasma concentration: predominantly distribution from the central compartment into peripheral tissues (α phase).
- Later slower decline: drug returns from peripheral compartments while elimination continues from the central compartment (β / terminal phase).
- In a three-compartment model a still slower terminal phase may reflect return from a deep, slowly equilibrating compartment.
- The observed plasma concentration-time curve is therefore the sum of several exponential processes, not a single exponential decay.
Inter-compartment movement
- Distribution between compartments is described by inter-compartmental clearances or transfer rate constants.
- Movement depends on tissue blood flow, membrane permeability, drug lipophilicity, ionisation, protein binding and tissue binding.
- At equilibrium, the steady-state apparent volume is the sum of model compartment volumes: Vss = V1 + V2 + … + Vn.
Clinical significance
| Clinical issue | Why the multi-compartment model matters |
|---|---|
| Single bolus offset | Clinical effect may terminate rapidly by redistribution away from the effect site before the drug is eliminated from the body. |
| Repeated doses / infusion | Peripheral compartments progressively fill; after stopping an infusion, drug can redistribute back to plasma and prolong effect. |
| Context-sensitive half-time | For many lipophilic drugs, offset becomes slower as infusion duration increases because tissue stores accumulate. |
| Plasma versus effect-site concentration | Clinical effect may lag behind plasma concentration because the effect site is not identical to the sampled plasma compartment. |
| Loading and maintenance dosing | Loading dose is influenced by distribution volume; ongoing dosing must account for both redistribution and elimination. |
Concentration-time curve
On a semi-log concentration-time plot, a multi-compartment drug shows an initial steep distribution phase followed by one or more progressively shallower terminal phases. Back-extrapolation can separate these exponential components mathematically.
b) Characteristics of drugs that fit this model (20%)
| Characteristic | Why it favours multicompartment behaviour | Examples |
|---|---|---|
| Lipophilic | Rapid entry into well-perfused tissues followed by redistribution into muscle/fat | Propofol, thiopentone, fentanyl |
| Large apparent Vd / tissue binding | Substantial drug leaves plasma and is stored in peripheral tissues | Fentanyl, digoxin |
| Rapid CNS/effect-site equilibration with slower tissue equilibration | Produces rapid onset and redistribution-driven offset after a bolus | Propofol, thiopentone |
| Infusion-duration dependent offset | Progressive saturation of peripheral compartments prolongs terminal washout | Fentanyl, propofol |
Exam focus
- Spend most of the answer on central/peripheral compartments, α distribution, terminal return/elimination, and clinical implications.
- Make clear that the early fall in plasma concentration is often redistribution rather than elimination.
- Link the model to single bolus versus infusion offset and effect-site lag.
Quick reference
Summary
| Feature | High-yield point |
|---|---|
| Model | Central compartment plus one or more peripheral compartments with inter-compartment transfer |
| Early phase | Rapid plasma fall mainly from redistribution (α phase) |
| Terminal phase | Return from peripheral tissues plus elimination from the central compartment |
| Clinical relevance | Explains bolus offset, infusion accumulation, context-sensitive behaviour and effect-site lag |
| Typical drugs | Lipophilic drugs with tissue distribution such as propofol, thiopentone and fentanyl |
Past papers
Exam appearances
| Exam | Exact exam wording | Candidate success |
|---|---|---|
| 2026A Q19 | a) Explain the multi-compartment pharmacokinetic model (80% of marks). b) Outline with examples, the characteristics of drugs that adhere to this model (20% of marks). | 23% |