Premium
Effects of KUR‐1246, a selective uterine relaxant, on transplacental passage and transmigration to milk
Author(s) -
Furihata Yoshio,
Kobayashi Mamoru,
Kojima Masami,
Kobayashi Kaoru,
Kawarabayashi Tatsuhiko,
Yamamoto Toshinori
Publication year - 2006
Publication title -
journal of obstetrics and gynaecology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 50
eISSN - 1447-0756
pISSN - 1341-8076
DOI - 10.1111/j.1447-0756.2006.00363.x
Subject(s) - transplacental , ritodrine , medicine , tocolytic , tocolytic agent , fetus , hydrochloride , uterine contraction , ephedrine , pregnancy , preterm labor , anesthesia , pharmacology , uterus , gestation , chemistry , biology , placenta , genetics , organic chemistry
Aim: To evaluate the safety of KUR‐1246 as a tocolytic agent, we determined the effects of its constant infusion on efficacy, transplacental passage, and transmigration to milk in pregnant or puerperal animals and compared them to the effects of ritodrine hydrochloride. Methods: A balloon method was used to evaluate the inhibitory effects of KUR‐1246 constant infusion on spontaneous uterine motility in pregnant rats. We also measured transplacental passage and transmigration to milk of KUR‐1246 in pregnant and/or puerperal animals. KUR‐1246 and ritodrine hydrochloride concentrations were quantified using a liquid chromatography‐tandem mass spectrometry method. Results: Constant infusion of KUR‐1246 and ritodrine hydrochloride clearly inhibited spontaneous uterine motility in vivo . The ED 50 value for KUR‐1246 was 1.1 mg/kg/min, a potency which was approximately 40‐fold greater than that of ritodrine hydrochloride. Transplacental passage (proportions of fetal plasma/maternal plasma) of KUR‐1246 in pregnant rats and/or guinea pigs were approximately one‐half to one‐third of that of ritodrine hydrochloride. Transmigration of KUR‐1246 to milk in puerperal rats disappeared by 48 h after injection. Conclusions: KUR‐1246 is a promising drug for the treatment of preterm labor in obstetric practice because it is as efficacious as currently used agents yet less likely to produce direct effects on the fetus.