Nifedipine concentration in maternal and umbilical cord blood after nifedipine gastrointestinal therapeutic system for tocolysis

Objective To determine nifedipine concentrations in maternal plasma at steady state, and maternal and umbilical cord plasma at delivery, after tocolysis with nifedipine gastrointestinal therapeutic system (GITS) tablets. Design Prospective clinical pharmacokinetic study. Setting Department of Obstetrics at the Zurich University Hospital. Population Pregnant women treated for threatened preterm labour. Methods GITS dosage titrated to clinical response (30-150 mg/day). Nifedipine concentrations by high-performance liquid chromatography and turbo ion spray tandem mass spectrometry. Main outcome measures Steady-state nifedipine concentrations in maternal blood and nifedipine concentrations in maternal and corresponding umbilical cord blood at delivery. Results Steady-state nifedipine concentrations (micrograms/l, mean +/- SE) were 54 +/- 6 (all doses, n = 31), 38 +/- 8 (60 mg/day, n = 13), and 92 +/- 12 (150 mg/day, n = 7) (P < 0.002). Umbilical cord and maternal concentrations both declined in a ln-linear regression with elimination half-lives of 20.4 and 17.4 hours. Linear regression showed a correlation between umbilical and maternal concentrations of 0.77 +/- 0.1 (n = 21, mean +/- SE). Conclusions Steady-state plasma nifedipine concentrations after repeated dosing with nifedipine GITS 30-150 mg/day in pregnant women with preterm labour do not exceed 100 micrograms/l; fetal levels are 77% of maternal levels.