title: Pharmacokinetics of modified slow-release oral testosterone over 9 days in normal men with experimental hypogonadism.
abstract: Oral administration of testosterone has potential use for the treatment of  hypogonadism. We have recently demonstrated that a novel formulation of oral  testosterone transiently normalized serum testosterone in a single-dose  pharmacokinetic study. In this report, we present the steady-state  pharmacokinetics of this formulation. Twelve healthy young men were rendered  hypogonadal with the gonadotropin-releasing hormone antagonist acyline (300  μg/kg subcutaneously) and administered 300 mg of oral testosterone 3 times  daily for 9 days. Serum testosterone, dihydrotestosterone (DHT), estradiol,  and sex hormone-binding globulin (SHBG) were measured before and 1, 2,  4, 5, 6, 8, 10, 11, 12, 14, 16, and 24 hours on the first and ninth day of  dosing. Before testosterone administration, all men had serum testosterone  under 75 ng/dL. Over day 1, the 24-hour average (geometric mean [%CV]) serum  total testosterone was 378 (45) ng/dL. This decreased to 315 (41) ng/dL after  9 days of continuous treatment (P = .1 compared with day 1). The  24-hour average serum SHBG was 27 (46) nmol/L on day 1 and was significantly  reduced to 19 (47) nmol/L by day 9 (P < .01). As a result, the  calculated free testosterone values were similar between day 1 and day 9: 8.7  (43) and 8.3 (37) ng/dL, respectively. DHT was in the reference range and  estradiol was slightly below on day 9. Oral testosterone (300 mg) dosed 3  times daily normalized serum testosterone in men with experimentally induced  hypogonadism after 9 days of dosing and significantly suppressed SHBG. This  formulation of oral testosterone may have efficacy for the treatment of  testosterone deficiency.
authors.affiliation: Center for Research in Reproduction and Contraception, Divisions of General Internal Medicine and Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington Medical School, Seattle, WA, USA.
authors.forename: Ada
authors.initials: A
authors.lastname: Lee
authors.forename: Katya
authors.initials: K
authors.lastname: Rubinow
authors.forename: Richard V
authors.initials: RV
authors.lastname: Clark
authors.forename: Ralph B
authors.initials: RB
authors.lastname: Caricofe
authors.forename: Mark A
authors.initials: MA
authors.lastname: Bush
authors.forename: Hui
authors.initials: H
authors.lastname: Zhi
authors.forename: Mara Y
authors.initials: MY
authors.lastname: Roth
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Page
authors.forename: William J
authors.initials: WJ
authors.lastname: Bremner
authors.forename: John K
authors.initials: JK
authors.lastname: Amory
mesh_terms: D000284:Administration, Oral; D000328:Adult; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013196:Dihydrotestosterone / Q000097:blood; D004958:Estradiol / Q000097:blood; D006801:Humans; D007006:Hypogonadism / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D009842:Oligopeptides; D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; C109238:acyline