A drug is 80% orally bioavailable, primarily due to hepatic first-pass metabolism. After IV administration, its apparent volume of distribution is 50 L (body weight 70 kg). After an oral dose achieving steady-state, the drug's Vd is most accurately described as:

• A 62.5 L — Vd increases proportionally with reduced bioavailability
• B 40 L — Vd decreases with first-pass metabolism
• C Cannot be determined without knowing plasma protein binding
• D 50 L — Vd is a drug property independent of route of administration ✓

Explanation

Volume of distribution (Vd) is an apparent pharmacokinetic parameter reflecting drug distribution between plasma and tissues — it is a property of the drug molecule (lipophilicity, protein binding, tissue affinity) and does not depend on the route of administration. Bioavailability affects the plasma concentration reached after a given dose but does not change the drug's inherent distribution characteristics. The same drug given IV or orally will have the same Vd once absorbed into the systemic circulation. Oral bioavailability affects the dose required to achieve a target Css but not Vd.

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

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