Foundational clinical pharmacokinetics relating volume of distribution and clearance
Core Principles & Analysis
In first-order linear pharmacokinetics, the elimination half-life is constant regardless of concentration and depends directly on apparent volume of distribution (Vd) and inversely on total systemic clearance (CL) according to t1/2 = (0.693 · Vd) / CL.
Multi-compartment drugs exhibit a biphasic plasma decay curve: a rapid initial α-phase half-life driven by redistribution from blood into peripheral tissues, followed by a slower terminal β-phase half-life governed by hepatic metabolism and renal excretion.
During repeated dosing or continuous infusion at a fixed interval, a drug reaches ~94% to 97% of its steady-state plasma concentration (Css) after 4 to 5 elimination half-lives, and likewise takes 4 to 5 half-lives to wash out after discontinuation.