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.