Figure 2 Pharmacokinetic/Pharmacodynamic Response (N=22) to ELIGARD® 22.5 mg – Patients Dosed Initially and at Month 3

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 (C) 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

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 (C) 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.

The mean steady-state volume of distribution of leuprolide following intravenous bolus administration to healthy male volunteers was 27 L. In vitro binding to human plasma proteins ranged from 43% to 49%.

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.

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.

No drug excretion study was conducted with ELIGARD®.

The majority of the patients (approximately 70%) studied in the clinical trials were age 70 and older.

The safety and effectiveness of ELIGARD® in pediatric patients have not been established (see CONTRAINDICATIONS ).

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

The pharmacokinetics of ELIGARD® in hepatically and renally impaired patients have not been determined

No pharmacokinetic drug-drug interaction studies were conducted with ELIGARD®.

One open-label, multicenter study was conducted with each ELIGARD® formulation (7.5 mg, 22.5 mg, 30 mg, and 45 mg) in patients with Jewett stage A though D prostate cancer who were treated with at least a single injection of study drug (Table 3). These studies eva luated the achievement and maintenance of castr