Pharmacokinetic study in women of three different doses of a new formulation of oral testosterone undecanoate, Andriol Testocaps.

ABSTRACT

STUDY OBJECTIVE: To assess the pharmacokinetic parameters of testosterone undecanoate after administration of a new oral formulation, Andriol Testocaps. DESIGN: Randomized, open-label, group-comparative, parallel-design, dose-proportionality study. SETTING: Clinical pharmacology unit. SUBJECTS: Forty-five healthy women without childbearing potential. INTERVENTION Two oral doses each of testosterone undecanoate 20, 40, or 80 mg were administered with meals, separated by a 12-hour dosing interval. MEASUREMENTS AND MAIN RESULTS: Serum concentrations of testosterone undecanoate were assayed by liquid chromatography with mass spectrometric detection, and of testosterone and 5alpha-dihydrotestosterone (DHT) by gas chromatography with mass spectrometric detection. Pharmacokinetic parameters were calculated using standard methods. Statistical analysis of dose proportionality was performed on the log(e)-transforms of dose-normalized area under the serum concentration-time curve from 0-12 hours (AUC(0-12)) and from zero to the sampling time of the last measurable concentration after administration of the second dose (AUC(0-t(last)), and maximum serum concentration after the first dose (C(max)l). For testosterone undecanoate, testosterone, and DHT, dose-related increases in plasma concentrations were found with increasing doses of testosterone undecanoate; maximum concentrations were found 5-7 hours after administration. Using baseline-corrected testosterone values, dose proportionality for testosterone was found for AUC(0-12), AUC(0-t)(last), and C(max)(l). After higher doses, plasma levels of testosterone undecanoate were higher and plasma levels of DHT lower than could be expected assuming dose proportionality. CONCLUSION: Serum testosterone levels are dose proportional after oral administration of two doses of a new formulation of testosterone undecanoate 20, 40, and 80 mg, Andriol Testocaps.