Problems related to bioequivalence and bioavailability for four antiepileptic drugs (AEDs) are reviewed. Bioequivalence and bioavailability of AEDs can be affected by many factors, including physicochemical characteristics of the agent, the dosage form, and physiological condition of the patient. In 1988, breakthrough seizures prompted an FDA investigation of one company's generic carbamazepine tablets. Results indicated that the manufacturer had changed its source of carbamazepine, which led to a wide range of dissolution characteristics for different lots of tablets. In two separate studies, clonazepam was shown to be more rapidly absorbed in patients with a normal gastric pH than in those with a higher-than-normal gastric pH. With phenytoin, which exhibits nonlinear pharmacokinetics, differences in the rate and extent of absorption can adversely affect the bioavailability of this agent. Finally, the bioequivalence of generic primidone was contested in an adolescent girl who appeared to experience more frequent seizures with a generic product than with a trade formulation. The effectiveness of a drug depends on complex interactions involving the drug, the drug product formulation, and the patient. Minimizing variability in the absorption process is particularly important with AEDs, because of their narrow therapeutic range.

 

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