title: Pharmacokinetics, safety and tolerability of three dosage regimens of buccal adhesive testosterone tablets in healthy men suppressed with leuprorelin.
abstract: We used a randomised, double-blind, crossover design to evaluate the pharmacokinetics, safety and tolerability of three doses of buccal adhesive testosterone tablets (BATT). Twenty-four healthy men, whose endogenous testosterone was suppressed to </=5.38 nmol/l with leuprorelin acetate, took BATT (10, 20 or 30 mg) daily for 10 days. There was a 4-day washout between treatments. Substantial testosterone absorption occurred from BATT, and mean serum testosterone, free testosterone and dihydrotestosterone (DHT) concentrations over 24 h showed circadian variation. Steady state was reached by day 5. Average 24-h concentrations for the three BATT doses were within the normal range for eugonadal men: testosterone 11.67-14.57 nmol/l, free testosterone 0.026-0.33 nmol/l and DHT 1.66-2.03 nmol/l. On all three doses, peak testosterone and free testosterone was reached 8-9 h after tablet application; DHT peaked about 1-2 h later, and declined more slowly. Hormone concentrations increased with BATT dose, but increases were less than dose-proportional. There was no evidence of testosterone accumulation. BATT was well tolerated.
authors.affiliation: Hammersmith Medicines Research, Central Middlesex Hospital, London NW10 7NS, UK.
authors.forename: K J
authors.initials: KJ
authors.lastname: Baisley
authors.forename: M J
authors.initials: MJ
authors.lastname: Boyce
authors.forename: S
authors.initials: S
authors.lastname: Bukofzer
authors.forename: R
authors.initials: R
authors.lastname: Pradhan
authors.forename: S J
authors.initials: SJ
authors.lastname: Warrington
mesh_terms: D000278:Administration, Buccal; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D019540:Area Under Curve; D002610:Cheek; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D013196:Dihydrotestosterone / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004562:Electrocardiography; D005881:Gingiva; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D016729:Leuprolide / Q000494:pharmacology; D008046:Lip; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects; D017060:Patient Satisfaction; D013739:Testosterone / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D006727:Hormone Antagonists; D013196:Dihydrotestosterone; D013739:Testosterone; D016729:Leuprolide