A drug follows two-compartment pharmacokinetics. After IV bolus, a biphasic plasma concentration decline is observed. The rapid initial decline (alpha phase) represents:

• A First-pass hepatic metabolism before drug reaches systemic circulation
• B Rapid renal filtration of free drug exceeding tubular reabsorption capacity
• C Drug distribution from central compartment (blood/highly perfused organs) to peripheral compartment (muscle, fat), not primarily elimination ✓
• D Saturation of plasma protein binding releasing free drug for rapid metabolism

Explanation

In two-compartment pharmacokinetics, IV bolus administration results in an initial rapid distributive phase (alpha phase) followed by a slower elimination phase (beta phase). The alpha phase reflects rapid distribution from the central compartment (blood and highly perfused tissues: liver, kidneys, lungs) to peripheral compartments (muscle, adipose, less perfused tissues), causing the sharp initial decline in plasma concentration. This is not elimination — the drug is redistributing. The beta phase reflects true elimination (metabolism and excretion) from the body. Clinically important examples include thiopental: its rapid central redistribution to muscle and fat explains why its short clinical duration of action (5-10 min) is far shorter than its elimination half-life (10-12 hours).

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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