MRCS PART A · APPLIED BASIC SCIENCES
Pharmacokinetics: clearance, concentration and half-life
Two selected foundations, with two foundation SBAs and two separately scored transfers. All quantities describe fictional compound Z in a linear, well-mixed one-compartment model. These are model calculations, not prescriptions, drug-specific targets or a complete pharmacology course. Sources checked.
2 topics · 4 original SBAs
1 · Balance input against elimination
Your task: Use clearance and concentration with consistent units to calculate a constant-infusion steady-state concentration.
Is clearance a mass of drug removed each hour?
No. Clearance CL has volume/time units. In this model elimination rate is CL × concentration: (L/h) × (mg/L) = mg/h.
Does a clearance of 5 L/h mean exactly 5 litres of fluid leave the body?
No. It is an equivalent drug-clearance volume, not a measurement of physical fluid loss.
What balances at constant-infusion steady state?
Input rate R equals elimination rate CL × C. Thus C at steady state = R/CL. Assume constant input, constant clearance, complete intravenous delivery and linear elimination; there is no absorption factor in this model.
If clearance changes, is the new steady concentration reached immediately?
No. Concentration evolves towards the new equilibrium. A calculated new steady value is not necessarily the current concentration.
What does the model actually assume?
With amount A and distribution volume V, C=A/V and dA/dt=R−CL×A/V. These stated equations define the fictional exercise; they do not establish the behaviour of every real drug.
What if elimination saturates or parameters vary over time?
The constant-clearance linear calculation may no longer apply. Do not extrapolate a model answer into an unverified real-drug regimen.
2 · Separate distribution volume from elimination capacity
Your task: Use t½=ln(2)×V/CL in the stated one-compartment model and distinguish the approach to equilibrium from its final concentration.
What sets the model's elimination half-life?
After input stops, first-order elimination gives t½≈0.693×V/CL. Litres divided by litres/hour gives hours. Here V and CL are constant and refer to the same concentration basis.
Can V be treated as a literal anatomical compartment?
No. Distribution volume relates model amount to measured concentration; an apparent volume need not equal a physical body-fluid space.
If V changes but CL stays fixed, what changes?
The elimination-rate constant CL/V changes. Half-life and the speed of approaching equilibrium change; the final constant-infusion concentration still follows R/CL.
Does unchanged final concentration mean the entire concentration–time curve is unchanged?
No. A shared final value can conceal different trajectories. Specify the observation time before comparing concentrations.
Is steady state reached exactly after a fixed number of half-lives?
The ideal model approaches equilibrium asymptotically. Starting from zero, the fraction reached after n half-lives is 1−(1/2)^n, not exactly 100% at a finite n.
Can this simple half-life describe every phase of a real drug's disposition?
No. Multicompartment distribution, changing parameters and nonlinear elimination require an appropriate model; do not equate a convenient model half-life with every observed clinical phase.