Evaluation of the phosphodiesterase 3 inhibitor ORG 9935 as a contraceptive in female macaques: initial trials

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)165-171
Number of pages7
JournalContraception
Volume81
Issue number2
DOIs
StatePublished - Feb 2010

Fingerprint

Female Contraceptive Agents
Phosphodiesterase 3 Inhibitors
Macaca
Primates
Haplorhini
Fertility
Pregnancy
Pregnancy Rate
Contraceptive Agents
Serum
Progesterone
High Pressure Liquid Chromatography
Placebos
Food
Injections
Therapeutics

Keywords

  • Contraception
  • Macaque
  • Meiosis
  • Oocyte
  • Phosphodiesterase inhibitor

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Evaluation of the phosphodiesterase 3 inhibitor ORG 9935 as a contraceptive in female macaques : initial trials. / Jensen, Jeffrey; Stouffer, Richard; Stanley, Jessica E.; Zelinski, Mary.

In: Contraception, Vol. 81, No. 2, 02.2010, p. 165-171.

Research output: Contribution to journalArticle

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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.",
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