Bioequivalence assessment of closerin capsule to dura seromycin capsule of cycloserine after a single oral dose administration to healthy male volunteers.

Author(s): Kim YG, Lee YJ, Lee ED, Lee SD, Kwon JW, Kim WB, Shim CK, Lee MG

Affiliation(s): College of Pharmacy, Seoul National University, Korea.

Publication date & source: 2000-10, Int J Clin Pharmacol Ther., 38(10):461-6.

Publication type: Clinical Trial; Randomized Controlled Trial

AIM: A bioequivalence study of the closerin capsules to the dura seromycin capsules was conducted. PATIENTS AND METHODS: Twenty-four healthy male Korean volunteers received each medicine at the cycloserine dose of 250 mg in a 2 x 2 crossover study. There was a one-week washout period between the doses. Plasma concentrations of cycloserine were monitored by a high-performance liquid chromatography for over a period of 72 hours after the administration. AUCinf (the area under the plasma concentration-time curve from time zero to time infinity) was calculated by the linear-log trapezoidal method. Cmax (maximum plasma drug concentration) and Tmax (time to reach Cmax) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUCinf and Cmax, and untransformed Tmax. RESULTS: There were no significant differences between the medications in AUCinf and Cmax. The point estimates and 90% confidence intervals for AUCinf (parametric) and Cmax (parametric) were, in point estimate (90% confidence interval), 0.992 (0.950 approximately 1.037) and 1.051 (0.965 approximatly 1.144), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration Guidelines. The corresponding value of Tmax was 0.000 (-0.250 approximatly 0.125). Moreover, the modified Pitman-Morgan's adjusted F test and equal variance test (one-sided) indicated that the 2 medications were comparable in intra- and inter-individual variability in cycloserine bioavailability. CONCLUSION: Therefore, these results indicate that the 2 medications of cycloserine are bioequivalent and, thus, may be prescribed interchangeably.