COMPARATIVE PHARMACODYNAMIC BIO- EQUIVALENCE OF TWO ORALLY ADMINISTERED FORMULATIONS OF ISOSORBIDE DINITRATE IN HEALTHY HUMAN SUBJECTS UNDER FASTING CONDITIONS

Abstract

BACKGROUND: Medical profession has realized the problem of wide variations in the therapeutic effectiveness of various brands of oral formulations containing the same active ingredient in equal amounts. A large number of preparations of isosorbide dinitrate are commercially available on the Indian Market. Manufacturers claim that their products are bioequivalent to the innovator's formulation but it may or may not be. So, the only way to verify these claims is to do a comparative bioequivalence study with the innovator drug formulation using confidence intervals. Hence the present study was undertaken to compare the pharmacodynamic bloequivalence of the only two marketed brands of 10 mg isosorbide dinitrate tablets in India in healthy, adult, male, human subjects under fasting conditions.

METHODS: The study was carried out as single dose, two treatment, two period, two- sequence crossover randomized trial on 8 healthy human subjects under fasting conditions.

RESULTS: All the 8 subjects successfully completed the study. There were no significant protocol deviations. The two drugs were well tolerated by the volunteers. Administration of the reference formulation (Isordil: Wyeth Lederle, Mumbai) showed a maximum reduction in systolic blood pressure of 32 3.96 mm of Hg (Emak 49 10.6 minutes. The area under the effect time curve at time i was 2491.875 + 555.826 mm. kr. Administration of the test formulation (Sorbitrate: Nicholas Piramal, Madhya Pradesh) showed a maximum reduction in systolic blood pressure of 30+ 4 mm of Hg at 45 +17.92 minutes. The area under the effect time curve at time 't' was found out to be 2295.625 + 456.829 mm.hr. The test to reference ratios for log transformed data of the test formulation for maximum reduction is the systolic blood pressure and area under the effect time curve were 91.93% and 93.77% respectively. The 90% confidence Interval for log transformed data for maximum reduction in the systolic blood pressure and area under the effect time curve were 83.91-100.7 and 81.12-111.27 respectively. There was no period, Sequence and formulation effect observed as indicated by the p values.

CONCLUSION: The two products were bioequivalent and can be safely substituted for the prophylaxis of angina pectoris and for the management of unstable angina pectoris.