First-Pass Metabolism Avoidance — FRCA Primary MCQ

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ModeratePharmacology - General PrinciplesFirst-Pass Metabolism AvoidanceFRCA Primary

Which option contains all of the listed routes that, when the drug is absorbed at its intended administration site, bypass hepatic first-pass metabolism caused by initial delivery in portal venous blood?

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Reveal the answer and explanation

Correct answer: D — Intramuscular and sublingual

Explanation lettering: B = shown as A · D = shown as B · A = shown as C · C = shown as D

C is correct. Drug absorbed from an intramuscular injection enters systemic capillaries and therefore does not initially pass through the portal circulation or liver. Drug absorbed through the sublingual mucosa similarly drains into systemic veins, bypassing hepatic first-pass metabolism; any portion that is swallowed may instead undergo gastrointestinal and hepatic presystemic metabolism. Oral administration commonly exposes absorbed drug to intestinal and hepatic first-pass metabolism, although this is not necessarily complete. Rectal administration is not a route of complete or reliable first-pass avoidance: upper rectal venous drainage enters the portal system, whereas middle and inferior rectal drainage enters the systemic circulation. Thus B omits sublingual administration, while D and E incorrectly treat rectal administration as uniformly bypassing portal delivery.

Reference: The Bioavailability of Drugs—The Current State of Knowledge, peer-reviewed review, 2023, https://www.medicines.org.uk/emc/product/13984/smpc