Comparative bioavailability study of two different nimesulide-containing preparations available on the Italian market

Objective: To determine the relative bioavailability of two nimesulide prep arations commercially available in Italy [the original product Aulin((R)) ( test preparation) and a generic product Nimesulide Dorom (reference prepara tion)] following single oral administration to healthy volunteers, since in vitro investigation has shown that the dissolution of nimesulide from Auli n((R)) is faster and more complete than from the generic product. Design: Randomised, two-way, cross-over study. Patients and Participants: 18 healthy male volunteers. Methods: Blood samples were withdrawn up to 24 hours after administration o f the two preparations, each containing 100mg of nimesulide, and the plasma concentrations of nimesulide and its main metabolite 4 ' -hydroxy-nimesuli de were quantified using a validated high performance liquid chromatography analytical method with ultraviolet detection. Results: For the area under the curve calculated from time zero to infinity (AUC(0-infinity)), arithmetic mean values for nimesulide were 19.93 (test preparation) and 9.32 (reference preparation) mg .h/L. The corresponding va lues for the metabolite 4 ' -hydroxy-nimesulide were 11.95 and 5.59 mg hn, respectively. The mean peak nimesulide plasma concentrations (C-max [value for the metabolite in parentheses] were 4.67 (1.63) mg/L for the test prepa ration and 1.60 (0.65) mg/L for the reference preparation. In addition, for nimesulide the ratio C-max/AUC(0-infinity) was calculated. The values obta ined were 0.25h(-1) (test) and 0.18h(-1) (reference). Statistical compariso ns of all three parameters (analysis of variance and confidence intervals) after logarithmic transformation showed significant differences and bioineq uivalence between the test and reference preparations. Conclusions: According to the results obtained in this study, the generic p roduct Nimesulide Dorom cannot be regarded as comparable to the original pr oduct Aulin((R)), and consequently the two preparations cannot be considere d interchangeable products according to the World Health Organization defin ition of generics.