Approvable generic carbamazepine formulations may not be bioequivalent in target patient populations

  • Tothfalusi L
  • Endrenyi L
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Abstract

OBJECTIVES: To demonstrate that with carbamazepine (CBZ), positive results of bioequivalence trials in healthy volunteers cannot be extrapolated to patients because metabolic enzyme induction fundamentally changes the pharmacokinetics of CBZ. METHODS: Bioequivalence trials were simulated assuming normal and induced metabolic clearance. The relevant pharmacokinetic parameters were drawn from published studies. RESULTS: The Cmax ratio depends on the clearance. A generic product which is fully compliant with the regulatory requirements in healthy volunteers could be non-bioequivalent in patients with enhanced elimination. CONCLUSION: A statement of bioequivalence of CBZ formulations, based on a single-dose study performed in healthy subjects, may not hold for a target patient population in the steady state.

Author-supplied keywords

  • Anticonvulsants/blood/ pharmacokinetics
  • Biological
  • Carbamazepine/blood/ pharmacokinetics
  • Computer Simulation
  • Drugs
  • Generic/administration & dosage/ pharmacoki
  • Humans
  • Models
  • Therapeutic Equivalency

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Authors

  • Laszlo Tothfalusi

  • Laszlo Endrenyi

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