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Approvable generic carbamazepine formulations may not be bioequivalent in target patient populations
Laszlo Tothfalusi1, Laszlo Endrenyi
1Semmelweis University, Budapest, Hungary.
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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