Pharmacokinetics of ritodrine in pregnant women and their neonates

[Speaker] Mayuko Soma:1
[Co-author] Ainari Konda:2, Yoichi Sasaki:1, Takashi Mishima:3, Mitsuaki Keira:3, Hiroshi Yoshida:3, Yuji Mukai:2, Takaki Toda:2, Nobuo Inotsume:2
1:Department of Pharmacy, Tenshi Hospital, Japan, 2:Hokkaido Pharmaceutical University School of Pharmacy, Sapporo, Japan, 3:Department of Obstetrics and Gynecology, Tenshi Hospital, Sapporo, Japan

 The highly selective β2-agonist ritodrine is the primary choice in Japan for the long-term treatment of women with threatened premature labor, whereas it is recommended for short-term management of up to 48 hours in Europe. The present study aimed to determine the clinical pharmacokinetics of ritodrine in pregnant patients and their neonates.
 Serum ritodrine concentrations were measured in 105 pregnant women and their singleton (n=67) or twin (n=38) neonates by HPLC or LC-MS/MS. Concentrations of umbilical serum ritodrine were also determined in 14 women and those of ritodrine conjugates were measured in nine women who were pregnant with twins. The Ethics Committee at Tenshi Hospital approved this study and all the women provided written consent to participate.
 The mean (± SD) infusion rates of ritodrine were 2.1±1.4 (range, 0.4-7.1) and 2.3±1.1 (range, 0.7-4.7) µg/min/kg in women carrying singletons and twins, respectively. Ritodrine clearance was significantly lower in women carrying twins than singletons (1.59±0.30 vs. 1.75±0.43 L/h/kg, p<0.001). Serum concentrations did not significantly differ between mothers of singletons and twins at preterm delivery (97.5±61.1 vs. 89.6±50.4 ng/mL), but remained significantly higher in mothers of twins than of singletons at term delivery (85.8±39.7 vs. 65.7±8.7 ng/mL, p<0.001). The mean (± SD) half-life of ritodrine elimination in newborns was 8.0±6.4 (range, 4.2-29.6) h. The amount of serum ritodrine required to maintain pregnancy was in the range of 21.8-126.0 ng/mL. The maternal-to-fetal transfer ratio of ritodrine was 1.15±0.26 (range, 0.75-1.64). The average serum concentrations of ritodrine sulfate and ritodrine glucuronide were 221.8±93.1 (81.6-489.0) and 251.5±91.2 (98.1-539.7) ng/mL, respectively.
 The clinical effectiveness of ritodrine should be evaluated and clinical pharmacokinetic parameters should be established based upon serum concentrations of ritodrine to determine the most effective use of this agent for pregnant women with threatened premature labor. The present findings will facilitate a detailed study of the safe and effective prevention of premature delivery using ritodrine.
Conflict of interest
 None of the authors have any potential conflicts of interest to declare regarding this presentation.
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