Correcting endogenous concentrations of testosterone influences bioequivalence and shows the superiority of TDS(R)-testosterone versus Androgel(R).

AIM Circulating concentrations of endogenous compounds such as testosterone, complicate the analysis of pharmacokinetic parameters when these compounds are administered exogenously. This study examines the influence of three correction methods of accounting for endogenous concentrations on the determination of bioequivalence between two testosterone formulations. METHODS 12 healthy males received 50 mg TDS-testosterone, TDS-placebo, and 50 mg Androgel in a randomized placebo controlled study. Three correction methods (1,2 and 3) to remove the influence of endogenous testosterone from the exogenous blood concentrations data were carried out before the calculation of the AUC and Cmax. The relative bioavailabilities between two treatments were then performed for the AUC and Cmax for all the corrected and uncorrected data. Correction 4 was performed on the AUC and the Cmax values and the average values were calculated for both active treatments. RESULTS The relative bioavailability comparison of the AUC and Cmax, showed that the TDS-testosterone and Androgel was bioequivalent by using uncorrected data (CI: 93 - 120%; AUC0-12 and 88 - 117%; Cmax). However, they were not bioequivalent when using all the corrections data ((Corr. 1; CI: 52 - 106%; AUC0-12 and 50 - 258%; Cmax), (Corr. 2; CI: 71 - 655%; AUC0-12 and 87 - 286%; Cmax), (Corr. 3; CI: 67 - 315%; AUC0-12 and 88 - 157%; Cmax)). TDS-testosterone also showed the higher AUC0-12 and Cmax compared to Androgel for uncorrected and all the Corrections 1, 2, 3 and 4. CONCLUSIONS Different results obtained in the relative bioavailability between TDS-testosterone and Androgel for uncorrected data and corrected data, suggests that correcting endogenous concentrations is important for the proper determination of bioequivalent for endogenous compounds such as testosterone.