Barusiban, an effective long-term treatment of oxytocin-induced preterm labor in nonhuman primates.
Preterm labor (PTL) affects up to 25% of human pregnancies in developing countries, but there are few therapeutic options. Based on the key role of oxytocin (OXT) in labor and parturition, OXT antagonists are a potentially useful class of drugs for PTL. Barusiban is a new selective, potent, and long-acting OXT receptor antagonist. In this study barusiban was given by continuous i.v. infusion to monkeys during the last 3 wk of pregnancy; the monkeys were also given daily doses of OXT to induce uterine contractions and simulate PTL. Barusiban effectively suppressed OXT-induced PTL-like contractions and prevented early delivery. In contrast, fenoterol (a beta2-adrenoceptor [beta2-AR] agonist used as a comparative control) did not inhibit uterine contractions in this model. Barusiban was particularly effective in maintaining low intrauterine pressure (IUP) near the end of pregnancy, which is when IUP in both OXT controls and fenoterol-treated females increased substantially. Although barusiban delayed the onset of labor, it did not prevent normal delivery. These data demonstrate the safety and efficacy of barusiban in reducing uterine contractility in response to repeated OXT challenge, and suggest that barusiban may be therapeutically effective in long-term treatment of PTL.
Reinheimer
Torsten M
TM
Ferring Pharmaceuticals A/S, International PharmaScience Center, Department of Non-Clinical Development, Copenhagen S, 2300 Denmark.
Chellman
Gary J
GJ
Resendez
John C
JC
Meyer
Julie K
JK
Bee
Walter H
WH
D000318:Adrenergic beta-Agonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D005260:Female; D005280:Fenoterol / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007743:Labor, Obstetric / Q000187:drug effects; D008252:Macaca fascicularis; D007752:Obstetric Labor, Premature / Q000188:drug therapy*; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010121:Oxytocin / Q000494:pharmacology; D011247:Pregnancy; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors*; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D009842:Oligopeptides; D018045:Receptors, Oxytocin; D005280:Fenoterol; D010121:Oxytocin; C517339:barusiban