Evaluation of the phosphodiesterase 3 inhibitor ORG 9935 as a contraceptive in female macaques: initial trials☆
Received 21 July 2009; received in revised form 28 September 2009; accepted 30 September 2009. published online 09 November 2009.
Abstract
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.
aDepartment of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR 97239, USA
bDivision of Reproductive Sciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA
Corresponding author. Department of Obstetrics and Gynecology, mail code UHN-70 Oregon Health and Science University, Portland, OR 97239, USA. Tel.: +1 503 494 4469; fax: +1 503 494 5083.
ABSTRACT