Synergistic effects of DL111-IT combined with mifepristone on termination of early pregnancy in rhesus monkeys

Abstract

The objectives of this study were to determine the synergistic effects of DL111-IT in combination with mifepristone (RU486) on termination of early pregnancy in rhesus monkeys. Pregnancy was confirmed by tactile sensation of pregnant uterus via anus with finger and ultrasound examination. Pregnancy termination was obtained with vaginal bleeding and abortion materials including fetuses and placentae after treatment. With multiple doses of DL111-IT or RU486 given alone between d24 and d50 of gestation, pregnancy arrests were obtained in 40% (2/5) of monkeys treated with DL111-IT intramuscularly (im) (25 mg · kg −1 · d −1 × 3 days), in 20% (1/5) of monkeys treated with 9 mg · kg −1 · d −1 × 2 days, and 4.5 mg · kg −1 on day 3 with RU486 intragastrically (ig). DL111-IT (25 mg · kg −1 on day 1, im) in combination with RU486 (the same treatment as above) resulted in 100% (10/10) termination of pregnancy and uterine bleeding lasted 6.6 ± 1.3 days. RU486 (as above treatment) in combination with misoprostal (Miso, 109 μg · kg −1 on day 3, ig) showed 71.4% (5/7) termination of pregnancy, and uterine bleeding lasted 12.9 ± 9.6 days. The synergistic effect of DL111-IT plus RU486 enhances termination of early pregnancy and significantly shortens the bleeding time than RU486 plus Miso does in rhesus monkeys.