Document Detail

Barusiban, a new highly potent and long-acting oxytocin antagonist: pharmacokinetic and pharmacodynamic comparison with atosiban in a cynomolgus monkey model of preterm labor.
MedLine Citation:
PMID:  15671092     Owner:  NLM     Status:  MEDLINE    
Preterm labor (PTL) represents a significant unmet clinical need that affects up to 20% of all pregnancies and is a leading cause of preterm delivery and associated neonatal morbidity and mortality. Therapeutic options are limited, with existing drug therapy (tocolytics) compromised by side effects and limited efficacy. Because oxytocin (OT) is likely to be involved causally in PTL, this study compared two OT receptor antagonists, barusiban and atosiban, for their tocolytic effects. OT was given to instrumented pregnant cynomolgus monkeys to induce contractions and simulate PTL. Barusiban or atosiban was then given iv (bolus or infusion) to evaluate inhibitory effects on uterine contractions, measured by telemetric recording of intrauterine pressure. Both antagonists had high efficacy (96-98% inhibition of intrauterine pressure) and rapid onset of action (0.5-1.5 h). Barusiban was three to four times more potent than atosiban, which was attributed to its higher affinity and selectivity for the OT receptor. Barusiban also had a much longer duration of action (>13-15 h, compared with 1-3 h for atosiban). The inhibitory effects of barusiban were reversible within 1.5-2.5 h by high-dose OT infusion. Overall, barusiban's improved potency, long duration of action, and reversibility may provide an improved tocolytic for treatment of PTL.
Torsten M Reinheimer; Walter H Bee; John C Resendez; Julie K Meyer; George J Haluska; Gary J Chellman
Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2005-01-25
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  90     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-04-07     Completed Date:  2005-05-31     Revised Date:  2008-09-03    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2275-81     Citation Subset:  AIM; IM    
Department of Non-Clinical Development, Ferring Pharmaceuticals, Copenhagen S, Denmark.
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MeSH Terms
Disease Models, Animal
Dose-Response Relationship, Drug
Hormone Antagonists / pharmacology*
Macaca fascicularis
Obstetric Labor, Premature / drug therapy*
Oxytocin / antagonists & inhibitors*
Tocolytic Agents / pharmacology*
Uterine Contraction / drug effects
Vasotocin / analogs & derivatives*,  pharmacokinetics,  pharmacology*
Reg. No./Substance:
0/Hormone Antagonists; 0/Tocolytic Agents; 50-56-6/Oxytocin; 9034-50-8/Vasotocin; 90779-69-4/atosiban

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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