d relatively constant (0.2 – 2.0 ng/mL).
Figure 2 Pharmacokinetic/Pharmacodynamic Response (N=22) to ELIGARD® 22.5 mg – Patients Dosed Initially and at Month 3
ELIGARD® 30 mg
The pharmacokinetics/pharmacodynamics observed during injections administered initially and at four months (ELIGARD® 30 mg ) in 24 patients with advanced prostate cancer is shown in Figure 3. Mean serum leuprolide concentrations following the initial injection rose rapidly to 150 ng/mL (Cmax) at approximately 3.3 hours after injection. After the initial increase following each injection, mean serum concentrations remained relatively constant (0.1 – 1.0 ng/mL).
Figure 3 Pharmacokinetic/Pharmacodynamic Response (N=24) to ELIGARD® 30 mg – Patients Dosed Initially and at Month 4
ELIGARD® 45 mg
The pharmacokinetics/pharmacodynamics observed during injections administered initially and at six months (ELIGARD® 45 mg) in 27 patients with advanced prostate cancer is shown in Figure 4. Mean serum leuprolide concentrations rose to 82.0 ng/mL and 102 ng/mL (Cmax) at approximately 4.5 hours following the initial and second injections, respectively. After the initial increase following each injection, mean serum concentrations remained relatively constant (0.2 – 2.0 ng/mL).
Figure 4 Pharmacokinetic/Pharmacodynamic Response (N=27) to ELIGARD® 45 mg - Patients Dosed Initially and at Month 6
There was no evidence of significant accumulation during repeated dosing. Nondetectable leuprolide plasma concentrations have been occasionally observed during ELIGARD® administration, but testosterone levels were maintained at castrate levels.
Distribution
The mean steady-state volume of distribution of leuprolide following intravenous bolus administration to healthy male volunteers was 27 L.1 In vitro binding to human plasma proteins ranged from 43% to 49%.
1Sennello LT et al. Single-dose pharmacokinetics of leuprolide in humans following intravenous and subcutaneous administration. J Pharm Sci 1986; 75(2): 158–160.
Metabolism
In healthy male volunteers, a 1-mg bolus of leuprolide administered intravenously revealed that the mean systemic clearance was 8.34 L/h, with a terminal elimination half-life of approximately 3 hours based on a two compartment model.1
No drug metabolism study was conducted with ELIGARD®. Upon administration with different leuprolide acetate formulations, the major metabolite of leuprolide acetate is a pentapeptide (M-1) metabolite.
Excretion
No drug excretion study was conducted with ELIGARD®.
Special Populations
Geriatrics
The majority of the patients (approximately 70%) studied in the clinical trials were age 70 and older.
Pediatrics
The safety and effectiveness of ELIGARD® in pediatric patients have not been established (see CONTRAINDICATIONS).
Race
In patients studied, mean serum leuprolide concentrations were similar regardless of race. Refer to Table 2 for distribution of study patients by race.
Table 2. Race Characterization of Study Patients Race ELIGARD®
7.5 mg ELIGARD®
22.5 mg ELIGARD®
30 mg ELIGARD®
45 mg
White 26 19 18 17
Black - 4 4 7
Hispanic 2 2 2 3
Renal and Hepatic Insufficiency
The pharmacokinetics of ELIGARD® in hepatically and renally impaired patients have not been determined
Drug-Drug Interact |
