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

作者：Toth****si Laszlo; Endrenyi Laszlo^*

来源：International Journal of Clinical Pharmacology and Therapeutics, 2013, 51(6): 525-528.

DOI：10.5414/CP201845

• bioequivalence
• antiepileptics
• carbamazepine
• autoinduction
• therapeutic equivalence

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 C-max 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.

• 出版日期2013-6