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SC MTX Bioavailability Advantage — SCE Rheumatology MCQ

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ModerateRheumatology PharmacologySC MTX Bioavailability AdvantageSCE Rheumatology

A 55-year-old woman with rheumatoid arthritis takes oral methotrexate 20 mg once weekly with folic acid. She has persistent nausea on the day of administration, and a switch to subcutaneous methotrexate is being considered. Which statement best describes the pharmacokinetic rationale for changing the route of administration?

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Reveal the answer and explanation

Correct answer: D — Mean oral bioavailability is approximately 70% and is variable, whereas subcutaneous bioavailability is nearly 100% and avoids variable gastrointestinal absorption.

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

B is correct. At low rheumatological doses, oral methotrexate has a mean bioavailability of approximately 70%, but absorption varies considerably between and within patients. Subcutaneous administration has nearly 100% bioavailability and avoids variable gastrointestinal absorption. Pharmacokinetic studies also show that oral systemic exposure tends to plateau at weekly doses of 15 mg or more, while subcutaneous exposure remains dose-proportional. Switching may therefore provide more predictable and greater exposure and may improve gastrointestinal intolerance, although nausea is not guaranteed to resolve. A and D incorrectly describe oral methotrexate as completely absorbed. C is wrong because subcutaneous, intramuscular and intravenous bioavailability are all nearly 100%. E reverses the established exposure advantage of subcutaneous administration.

Reference: Metoject PEN solution for injection in pre-filled pen, Summary of Product Characteristics, sections 4.2 and 5.2, current UK SmPC, https://www.medicines.org.uk/emc/product/11352/smpc