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Clozapine Pharmacokinetics — MRCPsych Paper B MCQ

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ModerateSchizophrenia & PsychosisClozapine PharmacokineticsMRCPsych Paper B

A 33-year-old woman with schizophrenia has taken clozapine 300 mg daily at a stable dose for 4 weeks. Administration of each evening dose has been supervised for the preceding 7 days. A correctly timed 12-hour trough plasma clozapine concentration is 0.18 mg/L. She smokes 30 cigarettes daily and takes no interacting medication. What is the most likely pharmacokinetic explanation for the low concentration?

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Correct answer: C — CYP1A2 induction by constituents of tobacco smoke

The correct answer is C. Constituents of combusted tobacco smoke induce CYP1A2, an important pathway in clozapine metabolism. This increases clozapine clearance and lowers its plasma concentration at a given dose. The heavy smoking history, stable dose, correctly timed trough sample and supervised administration make this the best explanation. Missed doses are unlikely after a week of supervised treatment. Clozapine is generally well absorbed, so malabsorption would require additional supporting clinical evidence. It is almost completely metabolised before excretion, with only trace unchanged drug in urine, making renal tubular secretion implausible. There is no information suggesting sample handling or analytical error. Smoking reduction or cessation can rapidly increase clozapine concentrations and requires clinical review and level monitoring.

Reference: Viatris Products Limited. Clozaril 100 mg Tablets: Summary of Product Characteristics, sections 4.5 and 5.2. Updated 13 March 2026. https://www.medicines.org.uk/emc/product/10290/smpc