Aim : To determine the pharmacokinetics of ritodrine in singleton and twin pregnancies. Methods : We treated 105 pregnant women(with singletons, n＝67 ; with twins, n＝38)with continuous infusion of ritodrine and then measured steady-state serum ritodrine concentrations using HPLC. Results : Ritodrine clearance(mean±SD)was significantly lower in women who delivered twins than in those who delivered singletons(1.59±0.30 vs. 1.75±0.43 L／h／kg ; p＜0.001). Serum ritodrine concentration did not differ significantly between women who delivered preterm singletons and those who delivered preterm twins (97.5±61.1 vs. 89.6±50.4 ng／mL ; p＝NS), but was significantly higher in women who delivered twins at term than in those who delivered singletons at term(85.8±39.7 vs. 65.7±38.7 ng／mL ; p＜0.001). Conclusion : Ritodrine clearance was lower in twin pregnancies than in singleton pregnancies. The dose of ritodrine administered to maintain pregnancy should be controlled taking into account singleton or twin pregnancy. (Jpn J Clin Pharmacol Ther 2013 ; 44(5) : 389-394)

Lissencephaly is one of the central nervous system anomalies of Miller-Dieker Syndrome (MDS). Fetuses with lissencephaly have an abnormal smooth brain with fewer folds and grooves that will be detected by ultrasounds or fetal magnetic resonance imaging (MRI) after 30 weeks of gestation. We report a fetus with lissencephaly diagnosed as Miller-Dieker Syndrome postnatally. G banded chromosome analysis revealed 45,X,psu dic(17;Y)(p13;p11.32).ish dic (17;Y)(LIS1-,RARA+, SRY+, DYZ3+) by G-banding analysis using high resolution banding technique. Fetal delayed cortical development will be the findings to perform further investigations including fluorescence in situ hybridization analysis for MDS, a 17p13.3 microdeletion syndrome, pre/postnatally. This will be the first case of MDS with unbalanced translocation between deleted short arm of chromosome 17 and Y chromosome.

This study aimed to clarify the individual elimination kinetics of serum ritodrine in women pregnant with twins and their twin neonates. Serum ritodrine concentrations in 10 twin pregnant women and their twin neonates were measured by liquid chromatography-tandem mass spectrometry(LC-MS／MS)using 100 mL of serum. The ritodrine elimination half-life in mothers was 5.0±2.2 (3.7-11.1) h［mean±SD (range)], while the halflives of ritodrine in the first and second newborns were 9.0± 8.4(4.2-29.6)and 7.2±4.3(4.3-13.2)h, respectively. Large individual differences in the half-life of ritodrine were observed in both mothers and their newborns. Since ritodrine remained in newborn serum for 24-48 h after birth, newborns need to be carefully monitored for ritodrine-related complications during this period.

No abstract

Ritodrine, a drug for the treatment of threatened premature labor, is a highly selective beta-2 agonist with the major metabolites of sulfate and glucuronide conjugates. This study investigated the continuous evaluation of the concentration of ritodrine conjugates in relation to the clinical course in twin pregnancy. The subjects were 9 twin-pregnancy mothers who delivered after receiving ritodrine treatment between April 2012 and December 2013. Serum ritodrine sulfate and glucuronide conjugates were deconjugated using their specific enzymes. Ritodrine concentration was measured by liquid chromatography-tandem mass spectrometry. The continuous infusion rate of ritodrine was 2.66 0.67 (0.8-3.54) µg/min/kg, and the average concentration of unchanged ritodrine was 118.8 33.2 (63.8-194.0) ng/mL. During the study period between week 32 and week 36 of gestation, the average ratio of unchanged ritodrine concentration and sulfate ritodrine conjugate concentration for weeks 32, 33, 34, 35, and 36 were 1.7, 1.9, 1.5, 1.7, and 1.7 not significant (N.S.), respectively. The average ratio of unchanged ritodrine concentration and glucuronide ritodrine conjugate concentration were 1.8, 2.2, 1.9, 1.8, and 2.1 (N.S.), respectively. No statistical difference was identified in the ratios of unchanged ritodrine concentration and sulfate or glucuronide ritodrine conjugate concentrations. Large individual differences were shown in the concentration of sulfate and glucuronide during the gestational period. No change in the ratio of the formation of ritodrine metabolites was identified as the gestational age progressed.