Termination of early pregnancy in the mouse, rat and hamster with DL111-ITand RU486

The effectiveness of DL111-IT and RU486 given alone and in combination for terminating early pregnancy was tested in the rat, mouse, and hamster. In t he mouse and rat, the combination of RU486 and DL111-IT is much more effect ive in terminating pregnancy than either of the two compounds used alone (s ingle or multiple treatment). A low-effective dose of DL111-IT in combinati on with a non-effective or a sub-effective dose of RU486, exerted additive or synergistic effects resulting in resorption of embryos and termination o f pregnancy. The serum progesterone concentrations were significantly suppr essed by these combinations when pregnancy was terminated. In the hamster, single treatment with DL111-IT plus RU486 exhibited a strong effect on inte rrupting early pregnancy. The ED,, of RU486 in combination of a non-effecti ve dose of DL111-IT was decreased to 163-fold lower dose than RU486 given a lone. It is concluded that in mouse, rat, and hamster, the synergistic acti on between DL111-IT and RU486 not only greatly enhances efficacy in termina ting pregnancy but also reduces substantially the dose required to produce this effect. (C) 2000 Elsevier Science Inc. All rights reserved.