Three-Compartment Model Alpha Phase — FRCA Primary MCQ

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ModeratePharmacology - General PrinciplesThree-Compartment Model Alpha PhaseFRCA Primary

Following an intravenous bolus, the plasma concentration of a drug is described by the three-compartment equation C(t) = Ae^−αt + Be^−βt + Ce^−γt, where α > β > γ. Which phase is dominated by the initial rapid distribution from the central compartment to rapidly equilibrating peripheral tissues such as muscle?

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Correct answer: B — Alpha phase

The alpha phase is the initial, steep component of the tri-exponential fall in plasma concentration. It is dominated by rapid distribution from the central compartment into rapidly equilibrating peripheral tissues, including muscle. This redistribution contributes to the early offset of effect after a single bolus of many intravenous anaesthetic drugs. The beta phase is the intermediate component and reflects slower intercompartmental redistribution together with elimination. The gamma phase is the terminal component, often governed by slow return of drug from poorly perfused or deep peripheral tissues plus elimination. There is no absorption phase after an intravenous bolus, because systemic bioavailability is immediate. Steady state requires a continuing input and is not a phase of post-bolus decline. Importantly, alpha, beta and gamma are macroexponential components rather than anatomically exclusive processes.

Reference: Parivar K, Wessén A, Widman M, Nilsson A. Pharmacokinetics of eltanolone following bolus injection and constant rate infusion. Journal of Pharmacokinetics and Biopharmaceutics. 1996;24:535–549. https://pubmed.ncbi.nlm.nih.gov/9300349/