Termination of early pregnancy in the mouse, rat and hamster with DL111-IT and 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 the mouse and rat, the combination of RU486 and DL111-IT is much more effective in terminating pregnancy than either of the two compounds used alone (single or multiple treatment). A low-effective dose of DL111-IT in combination with a non-effective or a sub-effective dose of RU486, exerted additive or synergistic effects resulting in resorption of embryos and termination of pregnancy. The serum progesterone concentrations were significantly suppressed by these combinations when pregnancy was terminated. In the hamster, single treatment with DL111-IT plus RU486 exhibited a strong effect on interrupting early pregnancy. The ED,, of RU486 in combination of a non-effective dose of DL111-IT was decreased to 163-fold lower dose than RU486 given alone. It is concluded that in mouse, rat, and hamster, the synergistic action between DL111-IT and RU486 not only greatly enhances efficacy in terminating pregnancy but also reduces substantially the dose required to produce this effect. (C) 2000 Elsevier Science Inc. All rights reserved.