Abstract
The protein binding and pharmacokinetics of diazepam, ACC-9653 (a phenytoin prodrug), and phenytoin were evaluated in nine healthy male volunteers following administration of diazepam and ACC-9653, alone or concomitantly, in a randomized crossover design. No significant differences were observed in the fraction unbound or pharmacokinetic parameters of ACC-9653, phenytoin, or diazepam when ACC-9653 was administered alone compared to concomitant administration with diazepam. The phenytoin fraction unbound increased significantly with increased concentrations of ACC-9653, indicating displacement of phenytoin from its binding sites by ACC-9653. ACC-9653 also demonstrated concentration dependent binding. The lack of a significant pharmacokinetic drug interaction between ACC-9653 and diazepam suggests that these drugs may be safely administered together, although this conclusion should be confirmed in the intended patient population.
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Hussey, E.K., Dukes, G.E., Messenheimer, J.A. et al. Evaluation of the Pharmacokinetic Interaction Between Diazepam and ACC-9653 (a Phenytoin Prodrug) in Healthy Male Volunteers. Pharm Res 7, 1172–1176 (1990). https://doi.org/10.1023/A:1015940527815
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DOI: https://doi.org/10.1023/A:1015940527815