In a two-compartment pharmacokinetic model after IV bolus dosing, the initial rapid decline in plasma concentration (alpha phase) represents:

• A Elimination of drug by the liver and kidney (true clearance)
• B First-pass metabolism reducing systemic availability
• C Renal tubular secretion and glomerular filtration of the drug
• D Distribution of drug from the central compartment (plasma/well-perfused tissues) into the peripheral compartment (muscle, fat, poorly perfused tissues) ✓

Explanation

In a two-compartment model, the plasma concentration-time curve after IV bolus shows a biexponential decline. The initial steep alpha (distribution) phase represents rapid equilibration of drug from the central compartment (plasma, highly perfused organs) to the peripheral compartment (muscle, fat, connective tissue). The subsequent slower beta (elimination) phase reflects true drug removal by metabolism and excretion once distribution equilibrium is achieved. Drugs like thiopental, lidocaine, and gentamicin exhibit this biexponential profile.

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

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