Evaluation of the phosphodiesterase 3 inhibitor ORG 9935 as a contraceptive in female macaques: initial trials.
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.
Jensen
Jeffrey T
JT
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR 97239, USA. jensenje@ohsu.edu
Stouffer
Richard L
RL
Stanley
Jessica E
JE
Zelinski
Mary B
MB
D000818:Animals; D003271:Contraceptive Agents, Female / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005298:Fertility / Q000187:drug effects*; D008252:Macaca fascicularis; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011247:Pregnancy; D013876:Thiophenes / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome
D003271:Contraceptive Agents, Female; D010726:Phosphodiesterase Inhibitors; D013876:Thiophenes; C097915:Org 9935