A Prospective, Double-blinded, Crossover Study to Determine the Equivalence of the Serum Levels and the Peak Level Toxicity of Diphenylhydantoin (EptoinR)

摘要

Context: In India, phenytoin is often prescribed as twice daily or thrice daily dosage schedules. In the West, this practice has been changed to a once daily regimen in most of the cases. Can we in India follow suit? Is our physical and genetic make up with regards to the phenytoin pharmacokinetics different? Does this necessitate a multiple dosing regimen to avoid adverse effects or even breakthrough seizures? Aims: This study was aimed at comparing 300mg once daily of phenytoin and 100mg tid of phenytoin in terms of its adverse effects, peak and trough serum concentrations. Settings and Design: Out patients attending the Neurology Department, Christian Medical College, Vellore, India. This was a prospective, randomized, double blinded, crossover study. Methods and Materials: Twenty-four patients were enrolled into the study. An informed consent was taken from them. Their liver and renal functions were checked. Their basal phenytoin levels were also estimated. Once the preliminary tests were found to be normal, the patients were inducted randomly into one of the two treatment arms, either 300mg once daily or 100mg thrice daily. Each arm was given for a 2 week period. Adverse effects were looked for and the peak and trough phenytoin concentrations were estimated. Statistical Analysis Used: The mean, SD and the P values were obtained by the Per Protocol and the ITT (Intention to Treat) analysis of the trough and peak serum levels by using Wilcoxon’s signed rank test. Results: One patient experienced an adverse effect in the once daily regimen as compared to no adverse effects in the tid regimen. The adverse effect was not consequential to the patient. Statistically, the trough concentrations were not significantly different between the regimens, although the peak concentrations of the once daily regimen were significantly higher. Conclusions: In conclusion, it can be said that the once daily regimen can be prescribed for Indian patients with epilepsy.