Pharmacokinetics of triptorelin after intravenous bolus administration in healthy males and in males with renal or hepatic insufficiency.

Abstract

AIMS:

Triptorelin is a gonadotropin-releasing hormone (GnRH) analogue with enhanced affinity for GnRH receptors and a prolonged half-life due to its resistance to enzymatic degradation. The sustained-release formulation of this molecule is advantageous in conditions requiring chronic hormone suppression.

METHODS:

This was an open study to determine the pharmacokinetics of a single i.v. bolus dose of 0.5 mg triptorelin acetate in four groups of six male subjects; namely in healthy subjects (Group I), in patients with varying degrees of renal insufficiency (Groups II and III), and in patients with hepatic insufficiency (Group IV).

RESULTS:

The maximum concentrations of triptorelin were found to be similar for all four study groups (geometric mean Cmax between 41.6 mg ml(-1) and 53.9 mg ml(-1)). The total clearance of triptorelin decreased with increasing renal impairment, and was even lower in patients with hepatic insufficiency (geometric mean CLtot: 210 ml min(-1), 113 ml min(-1), 86.8 ml min(-1) and 57.3 ml min(-1) for Groups I, II, III and IV, respectively). Serum triptorelin concentrations in all four groups were adequately described by a three-compartment model. The elimination half-life for patients with hepatic impairment was similar to that of patients with renal impairment (geometric mean t(1/2, z): 6.6 h, 7.7 h and 7.6 h for Groups II, III and IV, respectively), but significantly longer than in healthy volunteers (2.8 h for Group I). The first and second distribution half-lives were similar for the four groups studied, with geometric mean distribution half-lives of about 0.1 h (6 min) and 0.75 h (45 min), respectively.

CONCLUSIONS:

Although both renal and hepatic function are important for the clearance of triptorelin, the liver plays the predominant role in subjects suffering from some degree of renal impairment.

• Authors: F O Müller, J Terblanchè, R Schall, R van Zyl Smit, T Tucker, K Marais, G Groenewoud, H C Porchet, M Weiner, D Hawarden
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 44 Issue 4 Pg. 335-41 (Oct 1997) ISSN: 0306-5251 [Print] England
• PMID: 9354307 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antineoplastic Agents, Hormonal
• Luteolytic Agents
• Triptorelin Pamoate

Topics

• Adult
• Antineoplastic Agents, Hormonal (pharmacokinetics)
• Area Under Curve
• Biological Availability
• Half-Life
• Humans
• Liver Failure (blood, metabolism, urine)
• Luteolytic Agents (pharmacokinetics)
• Male
• Metabolic Clearance Rate
• Middle Aged
• Renal Insufficiency (blood, metabolism, urine)
• Triptorelin Pamoate (pharmacokinetics)