BIOEQUIVALENCE STUDY OF TWO BRANDS OF PHENYTOIN SODIUM 100MG FORMULATIONS IN HEALTHY ADULT MALE RABBITSAbstract
The objective of the study was to compare the bioavailability of a single oral 100 mg dose of two brands of phenytoin sodium formulations available in the Nepalese market. Formulation B was taken as test drug and compared with the innovator brand which was taken as reference standard. A randomized, two-way crossover study was done in six healthy adult male rabbits. All six rabbits received a single oral 100 mg dose of both the formulations with a two-week washout period between the formulations. Blood samples for plasma phenytoin levels were collected at 0.25, 1, 2, 4, 6, 8, 10, 12, 16, 24 hours. The pharmacokinetic parameters of the two brands of phenytoin sodium calculated were area under the concentration versus time curve from time zero to 24 hours (AUC 0–24), Area under the Curve from time zero to infinity (AUC0–∞), peak plasma concentration (Cmax) and time of peak concentration (tmax). Formulation B failed to comply in terms of Area under the Curve (AUC), an important pharmacokinetic parameter to test bioequivalency, which was tested at significance level 0.05. This showed that the test formulation is not bioequivalent with the innovator. Taken together, our preliminary findings suggest that further studies in a large population is needed before switching phenytoin brands once a patient is carefully titrated to a given phenytoin brand.
Saroj Nepal , Suhrid Banskota , Nirmal Marasini, Biki Gupta , Shyam Prasad Lohani , Shova Basnet and Bal Mukunda Regmi*
Institute of Medicine, Tribhuvan University, Kathmandu, Nepal
26 September, 2012
11 October, 2012
27 December, 2012
01 January, 2013