Leuprolide (Pharmacokinetics)

In this article, we will discuss Leuprolide (Pharmacokinetics). So, let’s get started.

Pharmacokinetics

Absorption

Leuprolide 7.5 mg for 1-Month Administration
Following a single injection of Leuprolide 7.5 mg for 1-month administration to patients, mean plasma measured concentrations were 20 ng/mL at 4 hours and 0.36 ng/mL at 4 weeks. However, intact leuprolide and an inactive major metabolite could not be distinguished by the assay which was employed in the study.

Leuprolide 22.5 mg for 3-Month Administration
Following a single injection of Leuprolide 22.5 mg for 3-month administration in patients, mean peak plasma concentrations were 48.9 ng/mL at 4 hours and then declined to 0.67 ng/mL at 12 weeks. Leuprolide appeared to be released at a constant rate following the onset of steady-state concentrations during the third week after dosing, providing steady plasma concentrations through the 12-week dosing interval. However, intact leuprolide and an inactive major metabolite could not be distinguished by the assay which was employed in the study. The initial burst, followed by a decline to a steady-state concentration, was similar to the release pattern seen with the monthly formulation.

Leuprolide 30 mg for 4-Month Administration
Following a single injection of Leuprolide 30 mg for 4-month administration in sixteen
orchiectomized prostate cancer patients, mean plasma concentrations were 59.3 ng/mL at 4 hours and then declined to 0.30 ng/mL at 16 weeks. Mean plasma concentrations from weeks 3.5 to 16 was 0.44 ± 0.20 ng/mL (range: 0.20-1.06). Leuprolide appeared to be released at a constant rate following the onset of steady-state concentrations during the fourth week after dosing, providing
steady plasma concentrations throughout the 16-week dosing interval. However, intact leuprolide and an inactive major metabolite could not be distinguished by the assay which was employed in the study. The initial burst, followed by a decline to a steady-state concentration, was similar to the release pattern seen with the other depot formulations.

Leuprolide 45 mg for 6-Month Administration
Following a single injection of Leuprolide 45 mg for 6-month administration in 26 prostate cancer patients, mean peak plasma concentration of 6.7 ng/mL was observed at 2 hours and then declined to 0.07 ng/mL at 24 weeks. Leuprolide appeared to be released continuously following the onset of steady-state concentrations during the third week after dosing providing steady plasma concentrations through the 24-week dosing interval. The initial burst, followed by
a decline to a steady-state concentration, was similar to the release pattern seen with the other depot formulations. In this study, mean plasma concentration-time profiles were similar after the first and second dose.

Distribution
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%.

Elimination
The mean systemic clearance of leuprolide following intravenous bolus administration to healthy male volunteers was 7.6 L/h, and terminal elimination half-life was approximately 3 hours based on a two compartment model.

Following administration of LUPRON DEPOT 3.75 mg to 3 patients, less than 5% of the dose was recovered as parent and M-I metabolite in the urine.

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