Clinical Pharmacokinetics

, Volume 39, Issue 1, pp 27–48 | Cite as

Clinical Pharmacokinetics of Goserelin

Review Articles Drug Disposition

Abstract

Goserelin is a synthetic decapeptide analogue of luteinising hormone-releasing hormone (LHRH). For experimental purposes it has been administered subcutaneously 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 eliminated from serum with a mean elimination half-life (t1/2β) of 4.2 hours in males and 2.3 hours in females. The shapes of the observed serum goserelin profiles following administration of the depots are primarily determined by the rate of goserelin release from the biodegradable lactide-glycolide copolymer matrix over periods of 1 or 3 months. There is no clinically relevant accumulation of goserelin during multiple administration of these depots.

Goserelin is extensively metabolised prior to excretion. Its pharmacokinetics are unaffected by hepatic impairment, but the mean t1/2β increases to 12.1 hours in patients with severe renal impairment. This suggests that the total renal clearance (renal metabolism and unchanged drug) is decreased in patients with renal dysfunction. It is unnecessary to adjust the dose or administration interval when the depot formulations are administered to elderly patients or to those with impaired renal or hepatic function.

Administration of a goserelin 3.6mg or 10.8mg depot results in an initial increase of luteinising hormone (LH) levels and in increases of serum testosterone or oestradiol levels in males and females, respectively. This is followed by a decrease in serum LH levels and suppression of testosterone or oestradiol to within the castrate or menopausal range, respectively. Subsequently, throughout treatment with goserelin depots, serum testosterone or oestradiol levels remain suppressed.

Clinical outcomes following treatment of patients with prostate cancer, breast cancer and benign gynaecological conditions with goserelin are described briefly.

Keywords

Prostate Cancer Testosterone Luteinising Hormone Endometriosis Serum Testosterone 

Notes

Acknowledgements

The author would like to thank the many colleagues and clinical trialists for their contributions to the AstraZeneca data on file which have been included in this review.

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© Adis Internotionol Limited 2000

Authors and Affiliations

  1. 1.Drug Metabolism and Pharmacokinetics DepartmentAstraZenecaMacclesfield, CheshireEngland

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