Pharmacokinetics of indomethacin in pregnancy

Clin Pharmacokinet. 2014 Jun;53(6):545-51. doi: 10.1007/s40262-014-0133-6.


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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Area Under Curve
  • Chromatography, High Pressure Liquid / methods
  • Female
  • Humans
  • Indomethacin / administration & dosage
  • Indomethacin / pharmacokinetics*
  • Mass Spectrometry / methods
  • Maternal-Fetal Exchange*
  • Placenta / metabolism*
  • Pregnancy
  • Tocolytic Agents / administration & dosage
  • Tocolytic Agents / pharmacokinetics*
  • Young Adult


  • Tocolytic Agents
  • Indomethacin