Pharmacokinetics of triptorelin after intravenous bolus administration in healthy males and in males with renal or hepatic insufficiency.
OBJECTIVE
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.
Müller
F O
FO
FARMOVS Research Centre for Clinical Pharmacology and Drug Development, University of the Orange Free State, Bloemfontein, South Africa.
Terblanchè
J
J
Schall
R
R
van Zyl Smit
R
R
Tucker
T
T
Marais
K
K
Groenewoud
G
G
Porchet
H C
HC
Weiner
M
M
Hawarden
D
D
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D006207:Half-Life; D006801:Humans; D017093:Liver Failure / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008186:Luteolytic Agents / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D051437:Renal Insufficiency / Q000097:blood / Q000378:metabolism* / Q000652:urine; D017329:Triptorelin Pamoate / Q000493:pharmacokinetics*
D018931:Antineoplastic Agents, Hormonal; D008186:Luteolytic Agents; D017329:Triptorelin Pamoate