Effect of the Concurrent LHRH Antagonist Administration with a LHRH Superagonist in Rats

Purpose. The purpose of this study was to investigate the effect of anovel LHRH antagonist, Orntide acetate, on the initial testosteroneelevation in rats during treatment with a LHRH superagonist,Leuprolide acetate.Methods. Thirteen groups of a rat animal model were administeredeither liquid Orntide or Orntide PLGA microspheres before or simultaneouslywith Leuprolide injections. Serum levels of testosterone weremonitored during the time course of the study using a radioimmunoas say method.Results. Administration of a single daily dose of liquid Orntide resultedin testosterone suppression within 6 h to levels below 0.5 ng/ml(castration level). However, combined administration of liquid Orntide andliquid Leuprolide did not have a significant effect on the initialtestosterone elevation in studied rats. Similarly, there was no effect when liquidOrntide was co-administered with Leuprolide microspheres. Administrationof Orntide microspheres 48 h before Leuprolide microspheressuppressed testosterone levels below the castration level within 24 h,however, did not prevent a rise in testosterone serum concentration uponadministration of Leuprolide microspheres. Also, a second testosteronepeak was observed between days 3 and 15 in the animals which weresimultaneously treated with Orntide microspheres and Leuprolidemicrospheres.Conclusions. Orntide acetate was found to be an effective LHRHantagonist with a rapid onset of pharmacological action and a shortbiological half-life. Administration of a single dose of liquid Orntideor Orntide microspheres, resulted in rapid testosterone suppressionwithout an initial elevation, as seen with LHRH superagonists. However,combined administration of Orntide and Leuprolide did not havean effect on the initial testosterone elevation in rats.