Exponential Decay
After a drug enters the bloodstream, the body eliminates it through metabolism (primarily hepatic) and excretion (primarily renal). For most drugs at therapeutic concentrations, elimination follows first-order kinetics: a constant fraction is removed per unit time. This produces exponential decay of plasma concentration, characterized by the half-life — the single most cited pharmacokinetic parameter.
The Sawtooth Pattern
With repeated dosing, each new dose adds to the drug remaining from previous doses. Plasma concentration follows a sawtooth pattern — sharp rises at each dose, exponential declines between doses. The peaks and troughs gradually climb until reaching steady state, where the amount administered per interval exactly equals the amount eliminated. This simulation visualizes the sawtooth accumulation in real time.
Reaching Steady State
Regardless of dose size or frequency, steady state is reached in approximately 5 half-lives. A drug with a 6-hour half-life reaches steady state in about 30 hours; one with a 24-hour half-life takes about 5 days. This principle governs loading dose calculations — when immediate therapeutic levels are needed, a loading dose bypasses the slow accumulation phase.
Clinical Dosing Decisions
The relationship between half-life and dosing interval determines fluctuation and accumulation. Dosing at one half-life intervals produces 2× accumulation with moderate fluctuation. Dosing much more frequently than the half-life produces high accumulation with minimal fluctuation (approaching a constant infusion). These trade-offs guide clinicians in selecting dosing regimens that maintain drug levels within the therapeutic window.