Bioequivalence Comparison of Two Drug-in-Adhesive Transdermal Nitroglycerin Patches.

Abstract

Plasma concentrations of nitroglycerin, 1,2-dinitroglycerin and 1,3-dinitroglycerin in 50 healthy male subjects who received single 24-h applications of two 0.6 mg/h drug-in-adhesive transdermal nitroglycerin patch formulations were compared for the purpose of establishing bioequivalence. The rates of appearance and elimination of nitroglycerin and both dinitro metabolites were the same for both patch treatments. The pharmacokinetic and statistical analyses indicated that the 20-cm(2) test patch met the current two one-sided t-test criteria for bioequivalence with the 30-cm(2) reference patch for nitroglycerin and both dinitro metabolites, even though the reference patch was 50% larger in size and contained 120% more nitroglycerin than the test patch. A likely explanation for the equivalence in drug delivery with a smaller patch is that the test patch maintained more intimate skin contact than did the reference patch. This study shows that strict bioequivalence criteria can be met with a highly variable drug such as nitroglycerin.