Comparison on Bioequivalence of Four Phenytoin Preparations in Patients with Multiple‐Dose Treatment

In previous pharmacokinetic studies on phenytoin, the authors found that a hybrid parameter, Vd/F, was much higher in Chinese subjects. It could be due to a lower bioavailability (F) of the tested phenytoin preparations and/or a higher volume of distribution (Vd) in Chinese. Therefore, the relative bioavailability of four phenytoin oral preparations, i.e. Dilantin (Taiwan), Dilantin (USA), Aleviatin (Taiwan), and Aleviatin (Japan), were compared in patients who regularly took Dilantin (Taiwan) with their phenytoin plasma level at steady state. Twenty‐four‐hour area under curve was measured by an HPLC method after substituting the daily dose with each 300‐mg dose of the test preparation. The plasma level resulted from Dilantin (USA) was found significantly higher than that from Dilantin (Taiwan). Similarly, Aleviatin (Japan) gave a significantly higher plasma level than Aleviatin (Taiwan). The study in part explained the unexpected high Vd/F of phenytoin in previous studies. 1992 American College of Clinical Pharmacology