Concentration of Sulfate and Glucuronide Conjugates of Ritodrine in Twin Pregnancy

• Published in: Biological & pharmaceutical bulletin 2017/06/01, Vol.40(6), pp.922-925
• Main Authors: Soma, Mayuko, Konda, Ainari, Fujieda, Satoko, Sasaki, Yoichi, Keira, Mitsuaki, Yoshida, Hiroshi, Mukai, Yuji, Toda, Takaki, Inotsume, Nobuo
• Format: Article
• Language: English
• Subjects: Adrenergic beta-2 Receptor Agonists; Adult; Age; conjugate; Conjugates; Enzymes; Evaluation; Female; Gestation; Gestational age; glucuronide; Glucuronides - blood; Humans; Labor; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Metabolites; Obstetric Labor, Premature - blood; Obstetric Labor, Premature - prevention & control; Pregnancy; Pregnancy, Twin - blood; ritodrine; Ritodrine - blood; Ritodrine - pharmacokinetics; Ritodrine - therapeutic use; serum concentration; Statistics; sulfate; Sulfates; Sulfates - blood; twin pregnancy; Twins
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b16-00818

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.