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Carbamazepine Autoinduction — MRCPsych Paper B MCQ

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HardMood DisordersCarbamazepine AutoinductionMRCPsych Paper B

A patient with bipolar I disorder starts carbamazepine. Pharmacokinetic sampling after a single dose shows an apparent elimination half-life of 36 hours. After 3 weeks of directly observed treatment with the same formulation and a constant daily dose, the elimination half-life is 18 hours and the dose-normalised trough concentration is lower. There are no concomitant medicines, and renal function, hepatic function, serum albumin and body weight remain unchanged. Which pharmacokinetic mechanism best explains these findings?

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Correct answer: E — Autoinduction of CYP3A4-mediated carbamazepine metabolism, increasing its clearance

The correct answer is E. Carbamazepine induces the hepatic enzyme systems responsible for its own metabolism, particularly CYP3A4. During repeated treatment this autoinduction increases clearance, shortening the elimination half-life from approximately 36 hours after a single dose to about 16–24 hours and lowering dose-normalised concentrations. CYP3A4 inhibition would produce the opposite pattern: reduced clearance, a longer half-life and higher concentrations. Renal elimination of unchanged carbamazepine is minor and would not normally account for this characteristic time-dependent change. Reduced protein binding is unsupported because albumin is stable and would not explain the marked shortening of half-life. An increased volume of distribution would tend to prolong rather than shorten half-life, and there is no evidence of fluid accumulation. Dose adjustment is not automatic; it should be guided by clinical response, tolerability and, where indicated, plasma concentrations.

Reference: Electronic Medicines Compendium, Tegretol 200 mg Tablets: Summary of Product Characteristics, sections 5.2 Pharmacokinetic properties and 4.5 Interactions, updated 2026. https://www.medicines.org.uk/emc/product/7845/smpc