Three-way, three-period, crossover bioequivalence study of single oral dose of three brands of 300 mg phenytoin sodium tablets marketed in India, on healthy Indian human volunteers

OBJECTIVE: To compare the bioavailability of two brands of phenytoin sodium tablets available in the Indian market using Eptoin™ as the reference. MATERIALS AND METHODS: A randomized, assessor-blind, three-way crossover design study was carried out over a period of 6 months after approval from the Institutional Review Board (IRB). Twenty-two healthy male participants received a single oral 300 mg oral tablet of either of the formulations with a 2-week washout. Blood samples were collected predose and at regular intervals postdose. Plasma phenytoin levels were estimated by high-performance liquid chromatography. Calculation of C(max), AUC(0-t), and AUC(0-∞) was done by the linear trapezoidal rule and 90-110% margin (90% confidence interval (CI)) was used to assess bioequivalence. RESULTS: Twenty volunteers completed the study. It was seen that the log-transformed values of C(max), AUC(0-t), and AUC(0-∞) of the test formulations were not within the specified limits. CONCLUSION: Bioinequivalence of available phenytoin brands indicates that switching brands could lead to variations in blood concentrations and thus impact safety and efficacy. If a brand switch is done for any reason, stringent drug-level monitoring is advised.