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

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 C_max 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 CL_tot: 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.