Pharmacokinetics of indomethacin in pregnancy.

ABSTRACT

BACKGROUND AND OBJECTIVES: Although indomethacin has been widely used for the treatment of preterm labor over the past 40 years, there are few reports regarding its pharmacokinetics in pregnant women. METHODS: This opportunistic study assessed the steady-state pharmacokinetics of indomethacin in pregnant subjects to whom an oral dose of 25 mg every 6 h was prescribed. Indomethacin concentrations in plasma and urine were analyzed by a validated high-performance liquid chromatography method with mass spectrometric detection. RESULTS: The mean area under the plasma concentration versus time curve at steady state (AUCss) was 1.91 ± 0.53 µg·h/mL, mean peak plasma concentration (C max) was 1.02 ± 0.49 µg/mL, and mean time to reach C max (t max) was 1.3 ± 0.7 h. The mean apparent clearance at steady state was 14.5 ± 5.5 L/h, which is higher than the apparent clearance reported in the literature for non-pregnant subjects. Indomethacin crosses the placenta; the mean fetal/maternal ratio from five sets of cord blood samples collected at delivery was 4.0 ± 1.1. CONCLUSIONS: Further studies are needed to determine whether any dose adjustments are necessary as a result of the increased clearance of indomethacin during pregnancy.