A drug has a half-life of 4 hours and is administered every 4 hours (one half-life interval). Assuming first-order kinetics and 100% bioavailability, at what fraction of the steady-state concentration will the drug be after 3 doses (12 hours)?

• A 75% of Css
• B 87.5% of Css ✓
• C 50% of Css
• D 93.75% of Css

Explanation

Steady state is reached after approximately 4–5 half-lives (97–100% Css). After 1 half-life (1 dose) one accumulates to 50% Css; after 2 half-lives (2 half-lives of dosing interval, but accumulation depends on dosing frequency): the general formula for accumulation fraction after n doses given every t1/2 is 1 - (1/2)^n. After 3 half-lives of dosing: 1 - (0.5)^3 = 1 - 0.125 = 0.875 = 87.5% Css. This applies when the dosing interval equals the half-life.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.