Pharmacokinetics of the gonadotropin-releasing hormone agonist buserelin after injection of a slow-release preparation in normal men.

The pharmacokinetics of the gonadotropin-releasing hormone (GnRH) agonist buserelin (D-Ser(BUt)6-GnRH-(1-9) nonapeptide-ethylamide, Hoe 766, CAS 57982-77-1) after injection of a slow-release preparation was investigated in 16 healthy young male volunteers. Eight volunteers received a buserelin implant of 3.3 mg and 8 volunteers one of 6.6 mg by subcutaneous injection. In order to prevent androgen deficiency symptoms caused by the GnRH agonist all volunteers were injected with an initial loading dose of 400 mg of the androgen 19-nortestosterone hexyloxyphenylpropionate one week prior to the buserelin administration, followed by injections of 200 mg once every three weeks up to week 23. Maximal buserelin serum levels were measured two days after injection of the implant. Following a slow decrease in serum concentrations up to week 8, serum buserelin had disappeared by week 14 in the 3.3 mg group and by week 17 in the 6.6 mg group. The areas-under-the-serum-concentration-versus-time-curves (AUCs) for the 3.3 and 6.6 mg implants were 691 +/- 60 ng x h/ml and 1050 +/- 102 ng x h/ml, respectively (p less than 0.01). The mean residence times (MRTs) of buserelin after administration of 3.3 mg and 6.6 mg buserelin implant were 4.7 +/- 0.4 and 4.1 +/- 0.3 weeks, respectively (p greater than 0.05). Urinary excretion of buserelin showed a similar pharmacokinetic profile. However, urinary buserelin was still detectable at very low concentrations by the end of the study, i.e. 29 weeks after implant injection.(ABSTRACT TRUNCATED AT 250 WORDS)