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Relationship between prolonged gestation and nifedipine pharmacokinetics in long-term tocolysis.

Miho TamuraSusumu MurataChihiro OtaShoko TanakaHitomi ArichikaDaiki HakunoNaoto OkadaKentaro UshijimaYasuhiro TsujiTakashi Kitahara
Published in: Basic & clinical pharmacology & toxicology (2023)
In this study, we examined the pharmacokinetics of nifedipine and investigated the maternal and foetal background factors that prolong pregnancy in pregnant women undergoing long-term tocolysis. This prospective observational study included 38 pregnant women hospitalised for threatened preterm labour and treated with nifedipine extended-release tablets in combination with intravenous ritodrine infusion. Maternal plasma nifedipine concentrations were determined using high-performance liquid chromatography. All patients were administered 20 or 40 mg/dose of nifedipine every 6 h at the time of blood sampling. The plasma trough concentration (C trough ) was 22.6 ± 17.3 ng/mL, maximum plasma concentration (C max ) was 30.9 ± 15.3 ng/mL, and time to maximum concentration (T max ) was 1.70 ± 1.10 h, as determined using noncompartmental analysis (NCA). The area under the curve for drug concentration (AUC tau ) was 152.3 ± 91.8 mg/L・h and oral clearance (CL/F) was 0.17 ± 0.08 L/h. Using logistic regression analyses, we identified the factors that predicted term delivery from 37 weeks to <42 weeks of gestation. Gestational age at admission and the AUC tau of nifedipine can predict term delivery. The AUC tau of nifedipine is a valuable regulatory predictor of term delivery in pregnant women undergoing long-term tocolysis.
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