评估磷酸二酯酶 3 抑制剂 ORG 9935 作为雌性猕猴避孕药的效果：初步试验。
Evaluation of the phosphodiesterase 3 inhibitor ORG 9935 as a contraceptive in female macaques: initial trials.
机构信息
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR 97239, USA.
出版信息
Contraception. 2010 Feb;81(2):165-71. doi: 10.1016/j.contraception.2009.09.015. Epub 2009 Nov 6.
BACKGROUND
The study was conducted to determine whether a phosphodiesterase (PDE) 3 inhibitor has potential as a novel contraceptive in primates.
METHODS
Regularly cycling adult female cynomolgus macaques of proven fertility (n=16) were treated for 7 months with placebo (controls) or the PDE3 inhibitor ORG 9935 as a daily food treat (150 mg/kg) or as a weekly depot injection (150 mg/kg, sc). After 1 month, a male of proven fertility was introduced into each group. Females underwent weekly monitoring of progesterone (P) and ultrasound evaluation for pregnancy if P remained elevated (1.0 ng/mL) >3 weeks. ORG 9935 values were evaluated using high-performance liquid chromatography.
RESULTS
Overall, the pregnancy rate in ORG 9935-treated monkeys (4/8, 50%) did not differ from controls (7/8, 88%; p=.5). However, no animal became pregnant in a cycle when the serum level of ORG 9935 exceeded 300 nmol/L. Moreover, two treated monkeys who mated throughout the treatment phase and did not conceive became pregnant within four cycles after stopping ORG 9935. The other two animals were discontinued prematurely from the protocol.
CONCLUSIONS
These results demonstrate that ORG 9935 may prevent pregnancy in primates at serum concentrations above 300 nmol/L and that the effect is reversible.
背景
本研究旨在确定磷酸二酯酶 (PDE)3 抑制剂是否有作为新型避孕药物在灵长类动物中应用的潜力。
方法
对 16 只具有生育能力的成年雌性食蟹猴进行常规周期循环，给予安慰剂（对照组）或 PDE3 抑制剂 ORG9935 作为每日食物处理（150mg/kg）或每周皮下注射（150mg/kg）。1 个月后，每组引入一只具有生育能力的雄性。如果孕激素 (P) 持续升高 (>3 周，1.0ng/mL)，则每周对女性进行 P 和超声检查以监测妊娠。使用高效液相色谱法评估 ORG9935 值。
结果
总体而言，ORG9935 治疗猴的妊娠率（4/8，50%）与对照组（7/8，88%）无差异（p=.5）。然而，当 ORG9935 的血清水平超过 300nmol/L 时，没有动物在一个周期中怀孕。此外，在治疗阶段交配但未怀孕的两只治疗猴在停止 ORG9935 后四个周期内怀孕。另外两只动物提前终止了方案。
结论
这些结果表明，ORG9935 可在血清浓度高于 300nmol/L 时预防灵长类动物怀孕，且该作用是可逆的。
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