The pharmacokinetics and pharmacodynamics of a new sustained-release leuprolide acetate depot compared to market references.

OBJECTIVE

The aim of this study was to compare the efficacy of Lutrate 3.75 and 7.5 mg depot to marketed references Lucrin 3.75 mg and Procrin 7.5 mg depot.

METHODS

20 healthy male volunteers were randomly assigned to receive 1 of 4 active single dose treatments in this double-blind, parallel-group pilot study. Leuprolide acetate and testosterone levels were quantified by radioimmunoassays.

RESULTS

The pharmacokinetic profile of leuprolide could be well-described by a 4-step release curve. Leuprolide levels were detectable 14 days longer after injection of the test formulations as compared to the reference products. The total AUC observed with 3.75 and 7.5 mg of the test product were approximately 1.5- and 2.2-fold higher, compared to the reference products, respectively. After the expected testosterone "flare-up" effect, castration was achieved in 4 of 4 subjects with the test formulations, 4 of 5 subjects with Procrin and 2 of 5 subjects with Lucrin. On average, castration lasted more than 1 month with both test formulations compared to 2 weeks with the reference products.

CONCLUSION

Sustained release of leuprolide from this new depot formulation suppressed testosterone levels at least as effectively and for a longer period of time than the reference products.