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 EptoinTM 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 Cmax, AUC0-t, and AUC0-∞ 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 Cmax, AUC0-t, and AUC0-∞ 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.