Clinical pharmacokinetics of goserelin

Goserelin is a synthetic decapeptide analogue of luteinising hormone-releas ing hormone (LHRH). For experimental purposes it has been administered subc utaneously as an aqueous solution, but for therapeutic use it is formulated as subcutaneous depots releasing goserelin over periods of 1 (3.6mg) or 3 (10.8mg) months. Pharmacokinetic data have been generated using a specific radioimmunoassay. When administered as a solution, goserelin is rapidly absorbed and elimina ted from serum with a mean elimination half-life (t1/2 beta) of 4.2 hours i n males and 2.3 hours in females, The shapes of the observed serum gosereli n profiles following administration of the depots are primarily determined by the rate of gosenlin release from the biodegradable lactide-glycolide co polymer matrix over periods of 1 or 3 months. There is no clinically releva nt accumulation of goserelin during multiple administration of these depots , Goserelin is extensively metabolised prior to excretion. Its pharmacokineti cs are unaffected by hepatic impairment, but the mean t1/2 beta increases t o 12.1 hours in patients with severe renal impairment. This suggests that t he total renal clearance (renal metabolism and unchanged drug) is decreased in patients with renal dysfunction. It is unnecessary to adjust the dose o r administration interval when the depot formulations are administered to e lderly patients or to those with impaired renal or hepatic function. Administration of a goserelin 3.6mg or 10.8mg depot results in an initial i ncrease of luteinising hormone (LPI) levels and in increases of serum testo sterone or oestradiol levels in males and females, respectively. This is fo llowed by a decrease in serum LH levels and suppression of testosterone or oestradiol to within the castrate or menopausal range, respectively. Subseq uently, throughout treatment with goserelin depots, serum testosterone or o estradiol levels remain suppressed. Clinical outcomes following treatment of patients with prostate cancer, boa st cancer and benign gynaecological conditions with goserelin are described briefly.