Carbamazepine induces its own metabolism via CYP3A4 (autoinduction), resulting in lower plasma levels after the first few weeks of therapy. This is an example of which pharmacokinetic phenomenon?
- A Zero-order kinetics where enzyme saturation is relieved
- B First-pass effect that increases progressively due to enterohepatic recirculation
- C Autoinduction — the drug induces the CYP enzyme responsible for its own metabolism, accelerating its clearance over time ✓
- D Saturation of plasma protein binding sites leading to increased free drug clearance
Correct answer: C. Autoinduction — the drug induces the CYP enzyme responsible for its own metabolism, accelerating its clearance over time
Explanation
Carbamazepine is a classic example of autoinduction. It activates the pregnane X receptor (PXR), which upregulates CYP3A4 expression. Over 3–5 weeks, CYP3A4 activity increases, accelerating carbamazepine's own clearance and reducing its half-life from ~36 hours initially to ~12–16 hours. This necessitates dose escalation and explains why initial effective doses become subtherapeutic. It also induces CYP3A4 metabolism of other drugs (OCP hormones, warfarin, cyclosporine), causing clinically important drug interactions.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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