Pharmacokinetic Study in Women of Three Different Doses of a New Formulation of Oral Testosterone Undecanoate, Andriol Testocaps

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 5α‐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 loge‐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‐tlast ), and maximum serum concentration after the first dose (C max1 ). 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‐tlast , and C max1 . 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.