NEW YORK (Reuters Health) - The experimental selective oxytocin receptor antagonist, barusiban, safely inhibits uterine contractions in a nonhuman primate model of preterm labor, Danish and US investigators report.
Barusiban has greater potency and longer duration of action than atosiban (Tractocile), a combined vasopressin and oxytocin receptor antagonist recently approved in Europe for preterm labor, the researchers note in the April issue of the Journal of Clinical Endocrinology and Metabolism.
Ferring Pharmaceuticals A/S in Copenhagen, which is developing barusiban, also developed and markets atosiban.
“Preterm labour is still an unmet clinical need, especially in the US where no uterine-relaxing drug is currently registered by the FDA,” Dr. Torsten M. Reinheimer from Ferring Pharmaceuticals noted in comments to Reuters Health.
He and his colleagues compared the tocolytic effects of an IV bolus of barusiban with that of atosiban in pregnant cynomolgus monkeys with oxytocin-stimulated contractions.
In this model, both agents were highly effective, inhibiting intrauterine pressure by 96% to 98%. Barusiban, however, was significantly more potent than atosiban, producing the same level of intrauterine pressure inhibition at roughly 4-fold lower blood levels due to its higher affinity and selectivity for the oxytocin receptor.
Moreover, the duration of action of barusiban -- more than 13 to 15 hours -- markedly exceeded that of atosiban at 1 to 3 hours. This could provide “important therapeutic advantages,” the authors say, since barusiban could be administered less often and nonparenterally.
Barusiban’s oxytocin inhibitory effects were rapidly reversible with high-dose oxytocin rescue therapy. This is also important, the authors note, in the event of an emergency cesarean section.
“Overall, barusiban’s improved potency, long duration of action, and reversibility may provide an improved tocolytic for treatment of preterm labor,” Dr. Reinheimer and colleagues conclude.
“This is an impressive proof of concept for barusiban,” Dr. Reinheimer said.
“We have already performed an extended proof of principle study in the same monkey model demonstrating barusiban’s effectiveness in long-term treatment of preterm labour,” the researcher told Reuters Health. In this study, “barusiban successfully suppressed oxytocin-induced labor for three weeks and prolonged pregnancy compared to an oxytocin control and fenoterol (beta2 adrenoceptor agonist).”
Source: J Clin Endocrinol Metab 2005;90:2275-2281. [ Google search on this article ]
MeSH Headings:Reproductive Control Agents: Tocolytic Agents: Chemical Actions and Uses: Chemical Actions: Chemicals and DrugsCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
