Excretion: Triptorelin is eliminated by both the liver and the kidneys. Following IV administration of 0.5 mg triptorelin peptide to 6 healthy male volunteers with a creatinine clearance of 149.9 mL/min, 41.7% of the dose was excreted in urine as intact peptide with a total triptorelin clearance of 211.9 mL/min. This percentage increased to 62.3% in patients with liver disease who have a lower creatinine clearance (89.9 mL/min). It has also been observed that the non-renal clearance of triptorelin (patient anuric, Clcreat=0) was 76.2 mL/min, thus indicating that the nonrenal elimination of triptorelin is mainly dependent on the liver (see Special Populations).

Special Populations

Renal and Hepatic Impairment: After an IV injection of 0.5 mg triptorelin peptide, the two distribution half-lives were unaffected by renal and hepatic impairment, but renal insufficiency led to a decrease in total triptorelin clearance proportional to the decrease in creatinine clearance as well as an increase in volume of distribution and consequently an increase in elimination half-life (Table 2). The decrease in triptorelin clearance was more pronounced in subjects with liver insufficiency, but the half-life was prolonged similarly in subjects with renal insufficiency, since the volume of distribution was only minimally increased.

Age and Race: The effects of age and race on triptorelin pharmacokinetics have not been systematically studied. However, pharmacokinetic data obtained in young healthy male volunteers aged 20 to 22 years with an elevated creatinine clearance (approximately 150 mL/min) indicates that triptorelin was eliminated twice as fast in this young population (see Special Populations, Renal and Hepatic Impairment) as compared to patients with moderate renal insufficiency. This is related to the fact that triptorelin clearance is partly correlated to total creatinine clearance, which is well known to decrease with age.

TABLE 2. PHARMACOKINETIC PARAMETERS (MEAN ±SD) IN HEALTHY VOLUNTEERS AND SPECIAL POPULATIONS

Pharmacokinetic Drug-Drug Interactions: No pharmacokinetic drug-drug interaction studies have been conducted with triptorelin (see PRECAUTIONS: DRUG INTERACTIONS).

Clinical Trials

TRELSTAR DEPOT was studied in a randomized, active control trial of 277 men with advanced prostate cancer. The clinical trial population consisted of 59.9% Caucasian, 39.3% Black, and 0.8% Other. There was no difference observed with triptorelin response between racial groups. Men were between 47 and 89 years of age (71 mean). Patients received either TRELSTAR DEPOT or an approved GnRH agonist monthly for 9 months. The primary efficacy endpoints were both achievement of castration by Day 29 and maintenance of castration from Day 57 through Day 253. Castration levels of serum testosterone ( ≤ 1.735 nmol/L) were achieved in 91.2% of TRELSTAR DEPOT patients at Day 29 and in 97.7% of patients at Day 57.

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