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.