Pharmacokinetic study in women of three different doses of a new formulation of oral testosterone undecanoate, Andriol Testocaps.
OBJECTIVE
To assess the pharmacokinetic parameters of testosterone undecanoate after administration of a new oral formulation, Andriol Testocaps.


METHODS
Randomized, open-label, group-comparative, parallel-design, dose-proportionality study.


METHODS
Clinical pharmacology unit.


METHODS
Forty-five healthy women without childbearing potential.


METHODS
Two oral doses each of testosterone undecanoate 20, 40, or 80 mg were administered with meals, separated by a 12-hour dosing interval.


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.


CONCLUSIONS
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.
Department of Drug Metabolism and Kinetics, Organon, Oss, The Netherlands.
Natalie S
NS
Houwing
Frans
F
Maris
Peter G
PG
Schnabel
Wilma M
WM
Bagchus
D000284:Administration, Oral; D000368:Aged; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D013196:Dihydrotestosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000378:metabolism; D008875:Middle Aged; D013739:Testosterone / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors
D002214:Capsules; D013196:Dihydrotestosterone; D013739:Testosterone; C010792:testosterone undecanoate