Objective: To evaluate the safety of KUR-1246 as a tocolytic agent, we examined the effects of its long term infusion on respiratory and cardiovascular systems and general metabolism in pregnant sheep and their fetuses. Design: Animal experiment with chronically instrumented ewes and their fetuses. Setting: Center for animal experiments, Hokkaido University School of Medicine, Japan. Sample: Eight Suffolk ewes at 117 to 120 days of gestation. Methods: At 120-124 days of gestation, ewes (n = 4) were infused intravenously for 24 hours with KUR-1246 at 0.03 μg/kg/minute, a dose that completely inhibits oxytocin-induced uterine contractions in pregnant sheep. The controls received saline instead (n = 4). Statistical comparisons were carried out by repeated-measures ANOVA followed by Dunnett's test. Main outcome measures: Maternal and fetal values of heart rate, blood pressure, plasma electrolytes, glucose, insulin and non-esterified fatty acid levels, and blood gases and lactate level. Results: The maternal plasma levels of KUR-1246 increased and reached a plateau at 15 hours or later from the start of the infusion, whereas the fetal levels of it were below the lower limit of quantification (0.1 ng/ mL) throughout the experiment. Significant differences over time between the ewes that had received with KUR-1246 and the controls were found for the following parameters: maternal heart rate, blood lactate, plasma glucose, and plasma insulin levels, and fetal plasma glucose and plasma insulin levels (P < 0.05). In the KUR-1246 treated ewes, significant changes from the pre-infusion value were detected in maternal blood lactate and fetal plasma glucose levels within 6 hours from the start of the infusion (P < 0.05). No significant differences were observed in other parameters in either ewes or fetuses. Conclusion: The physiologic changes induced by a 24-hour infusion of KUR-1246 were transient and considered to be within the compensatory capacity in both pregnant ewes and their fetuses, suggesting that KUR-1246 is a potentially safe tocolytic agent for use by long term infusion.
|Number of pages||6|
|Journal||BJOG: An International Journal of Obstetrics and Gynaecology|
|Publication status||Published - 2005 Jan|
ASJC Scopus subject areas
- Obstetrics and Gynaecology