Assessment of fertility in male rats after extended chemical castration with a GnRH antagonist
Journal Title: The AAPS Journal - Year 2004, Vol 6, Issue 1
Abstract
The purpose of this study was to assess whether male rats whose testosterone levels were suppressed to castration levels (<0.5 ng/mL) for a 1-year period by the sustained delivery of orntide acetate, a GnRH antagonist, would return to fertility (ie, produce offspring) after serum testosterone returned to control levels. Male rats comprising a treatment group (orntide microspheres, dose=27 mg/kg/y), a vehicle control group, and a control group of proven male breeders were used. For the treatment and vehicle control groups, serum orntide and testosterone levels were monitored at periodic intervals for 14 months from the initiation of treatment. After serum testosterone levels returned to vehicle control levels and orntide serum levels were no longer discernible for the treated group, each of the animals was housed with 2 drug-naive, female, proven breeders. All the breeder females produced offspring with the exception of 1 female housed with a male rat from the treatment group and the 2 females housed with a single male rat from the vehicle control group. The mean size and weight of the litters from each group were not statistically different. Further, fertility of the offspring from each group was assessed. The male and female offspring studied were all shown to be fertile. The results suggest that lack of fertility due to testosterone suppression in male rats is reversible after cessation of treatment with the GnRH analog, orntide.
Authors and Affiliations
Susan S. D'Souza, Francesca Selmin, Santos B Murty, Wei Qiu, BC Thanoo, Patrick P DeLuca
Keywords
Related Articles
- EP ID EP681956
- DOI 10.1208/ps060110
- Views 88
- Downloads 0
Nanoparticles in Vaccine Delivery
Physiologically Based Pharmacokinetic Modelling of Drug Penetration Across the Blood–Brain Barrier—Towards a Mechanistic IVIVE-Based Approach
Predicting the penetration of drugs across the human blood–brain barrier (BBB) is a significant challenge during their development. A variety of in vitro systems representing the BBB have been described, but the...
Mesenchymal Stromal/Stem Cell and Minocycline-Loaded Hydrogels Inhibit the Growth of Staphylococcus aureus that Evades Immunomodulation of Blood-Derived Leukocytes
The online version of this article (doi:10.1208/s12248-015-9728-6) contains supplementary material, which is available to authorized users.
Modelling and PBPK Simulation in Drug Discovery
Physiologically based pharmacokinetic (PBPK) models are composed of a series of differential equations and have been implemented in a number of commercial software packages. These models require species-specific and comp...
Amphiphilic star-like macromolecules as novel carriers for topical delivery of nonsteroidal anti-inflammatory drugs
The objective of this study was to evaluate amphiphilic star-like macromolecules (ASMs) as a topical drug delivery system. Indomethacin, piroxicam, and ketoprofen were individually encapsulated into the ASMs using coprec...