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• W2072007595 abstract "OBJECTIVE: To determine whether the phosphodiesterase (PDE) 3 inhibitor ORG 9935 has potential as a contraceptive in primates. DESIGN: Nonhuman primate, in vivo controlled experiment. MATERIALS AND METHODS: Regularly-cycling adult female cynomolgus macaques of proven fertility (n=16) were divided into 2 equal harems, and group-housed in separate but identical indoor facilities. During a pretreatment phase, ovulation was confirmed by monitoring cycle length and serum hormone levels, and animals were conditioned to enter a training tunnel for daily vaginal swab examinations to detect menstruation or mating. Monkeys were treated for 7 months with either a placebo oral food treat (controls) or the PDE 3 inhibitor ORG 9935 as a daily food treat (150 mg/kg), or as a weekly subcutaneous injection (150 mg/kg in CAPTEX 355 (Abitec)) if they refused oral dosing. After one month on study drug or placebo, a male monkey of proven fertility was introduced into each harem for 6 months. Females underwent weekly monitoring of progesterone (P) and ultrasound evaluation for pregnancy if P remained elevated for more than 3 weeks. Pregnant animals were removed from the group and underwent medical abortion. ORG 9935 values were evaluated using High-Performance Liquid Chromatography. RESULTS: In the control group, 7/8 (88%) monkeys became pregnant following one to six mated cycles of exposure. Although the pregnancy rate in ORG 9935-treated monkeys (4/8; 50%, p = 0.5) did not differ from controls, 2 treated monkeys were mated during all 6 ovulatory cycles and did not conceive. Both of these animals became pregnant within 4 cycles after stopping ORG 9935. The other 2 animals were discontinued prematurely from the protocol for medical reasons. No animal became pregnant in a cycle when the serum level of ORG 9935 exceeded 300nmol/l. CONCLUSIONS: These preliminary results demonstrate that ORG 9935 may prevent pregnancy in primates at serum concentrations above 300 nmol/l, and that the effect is reversible. Further work directed toward drug toxicity, availability and administration are warranted to determine whether PDE 3 inhibitors have potential clinical use as contraceptives in women." @default.
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• W2072007595 date "2008-09-01" @default.
• W2072007595 modified "2023-09-30" @default.
• W2072007595 title "The phosphodiesterase 3 inhibitor ORG 9935 prevents pregnancy in cynomolgus macaques" @default.
• W2072007595 doi "https://doi.org/10.1016/j.fertnstert.2008.07.631" @default.
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