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

L. Tóthfalusi, Laszlo Endrenyi

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)525-528
Number of pages4
JournalInternational Journal of Clinical Pharmacology and Therapeutics
Volume51
Issue number6
DOIs
Publication statusPublished - Jun 2013

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Therapeutic Equivalency
Health Services Needs and Demand
Carbamazepine
Healthy Volunteers
Pharmacokinetics
Enzyme Induction

Keywords

  • Antiepileptics
  • Autoinduction
  • Bioequivalence
  • Carbamazepine
  • Therapeutic equivalence

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

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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.",
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AU - Endrenyi, Laszlo

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AB - 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.

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