Oral testosterone in oil plus dutasteride in men: a pharmacokinetic study.
Testosterone (T) is not administered orally, because it has been reported to be rapidly metabolized by the liver. We hypothesized that sufficient doses of T or T enanthate (TE), administered orally in oil, would result in clinically useful elevations in serum T. We also hypothesized that coadministration of dutasteride (D) with T or TE would minimize increases in serum DHT seen previously with oral administration. Therefore, we conducted a pharmacokinetic study of oral T and TE in oil, with and without concomitant D, in normal men whose T production had been temporarily suppressed by the GnRH antagonist acyline. Thirteen healthy men (mean age, 24 +/- 6 yr) were enrolled and assigned to oral T (n = 7) and oral TE (n = 6) groups and were administered 200, 400, or 800 mg of either T or TE in sesame oil in the morning on 3 successive days 24 h after receiving acyline. Blood samples for measurement of serum T and dihydrotestosterone were obtained before T or TE administration and 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 h after administration. Subjects were then administered D for 4 d before repeating the sequence of T or TE doses with D. Serum T was significantly increased in a dose-dependent fashion with the administration of oral T or TE in oil. Coadministration of D with oral T or TE significantly increased the 24-hr average serum T levels compared with administration of T or TE alone [average serum T after 400 mg dose, 8.7 +/- 3.0 nmol/l (T) and 8.3 +/- 5.7 nmol/l (TE) vs. 16.1 +/- 5.8 nmol/l (T +D) and 15.0 +/- 8.8 nmol/l (TE + D); P < 0.05 for T vs. T and D]. The administration of oral T or TE in oil combined with D results in unexpected and potentially therapeutic increases in serum T. Additional studies of this combination as a novel form of oral androgen therapy are warranted.
Amory
John K
JK
Center for Research in Reproduction and Contraception, Division of General Internal Medicine, University of Washington Medical School, Box 356429, 1959 NE Pacific Street, Seattle, Washington 98195, USA. jamory@u.washington.edu
Bremner
William J
WJ
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001378:Azasteroids / Q000008:administration & dosage*; D013196:Dihydrotestosterone / Q000097:blood; D000068538:Dutasteride; D004958:Estradiol / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*
D001378:Azasteroids; D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; C004648:testosterone enanthate; D000068538:Dutasteride