BIOEQUIVALENCE EVALUATION OF THE METABOLITES 1,2-GLYCERYL AND 1,3-GLYCERYL DINITRATE OF 2 DIFFERENT GLYCERYL TRINITRATE PATCHES AFTER 12-H USAGE IN HEALTHY-VOLUNTEERS

In the course of this study both the bioavailability and main pharmaco kinetic parameters of the glyceryl trinitrate (GTN, CAS 55-63-0) metab olites 1,2 and 1,3-glyceryl dinitrate (1,2-GDN and 1,3-GDN) were to be determined following transdermal application of a glyceryl trinitrate test patch (Deponit(R) 5) and an already marketed reference patch. Fo r this purpose, both patches were examined in healthy volunteers accor ding to a randomized two-way cross-over design, blood samples were wit hdrawn up to 15 h after start of patch application and the plasma conc entrations of both metabolites were quantified using a GC/MS method. T he investigation showed the following results: Metabolite 1,2-glyceryl dinitrate: For the area under the curve from time 0 to the last quant ifiable sample (AUC(O-T-last) arithmetic mean values of 23.77 h.ng/ml (test patch) and 27.83 h.ng/ml (reference patch) were found. The corre sponding peak plasma levels were 2.45 ng/ml and 2.93 ng/ml, respective ly; they were reached after 6.4 h (test patch) and 8.31 h (reference p atch). Metabolite 1,3-glyceryl dinitrate: The arithmetic mean values f or AUC(O-T-last) were 3.32 h.ng/ml (test patch) and 3.81 h.ng/ml (refe rence patch). The maximum plasma levels were 0.35 ng/ml and 0.41 ng/ml for the test and reference preparation, reached after 6.4 h and after 7.86 h, respectively. The statistical comparison (ANOVA, confidence i ntervals) showed bioequivalence between both patches concerning the me tabolites investigated. The typical side effects known after nitrate t herapy also occurred in the course of this study.