Effects of KUR-1246, a selective uterine relaxant, on transplacental passage and transmigration to milk.
OBJECTIVE
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 ED50 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.
Furihata
Yoshio
Y
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Kobayashi
Mamoru
M
Kojima
Masami
M
Kobayashi
Kaoru
K
Kawarabayashi
Tatsuhiko
T
Yamamoto
Toshinori
T
D000081:Acetamides / Q000032:analysis / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008431:Maternal-Fetal Exchange; D008892:Milk / Q000737:chemistry*; D009281:Naphthalenes / Q000032:analysis / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012312:Ritodrine / Q000494:pharmacology; D015149:Tocolytic Agents / Q000032:analysis / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
D000081:Acetamides; D009281:Naphthalenes; D015149:Tocolytic Agents; C425888:bedoradrine; D012312:Ritodrine