Pharmacokinetics of Indomethacin in Pregnancy

• Published in: Clinical pharmacokinetics Vol. 53; no. 6; pp. 545 - 551
• Main Authors: Rytting, Erik, Nanovskaya, Tatiana N., Wang, Xiaoming, Vernikovskaya, Daria I., Clark, Shannon M., Cochran, Marlo, Abdel-Rahman, Susan M., Venkataramanan, Raman, Caritis, Steve N., Hankins, Gary D. V., Ahmed, Mahmoud S.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2014; Adis International; Springer Nature B.V
• Subjects: Administration, Oral; Adolescent; Adult; Area Under Curve; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; Female; General pharmacology; Humans; Indomethacin - administration & dosage; Indomethacin - pharmacokinetics; Internal Medicine; Mass Spectrometry - methods; Maternal-Fetal Exchange; Medical sciences; Medicine; Medicine & Public Health; Original Research Article; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacotherapy; Placenta - metabolism; Pregnancy; Tocolytic Agents - administration & dosage; Tocolytic Agents - pharmacokinetics; Young Adult; Cord Blood Sample; Cord Blood; Indomethacin; Oligohydramnios; Short Cervix; Non steroidal antiinflammatory agent; Pregnancy; Human; Prostaglandin-endoperoxide synthase; Enzyme; Indometacin; Indoleacetic acid derivatives; Enzyme inhibitor; Female; Oxidoreductases; Pharmacokinetics; Tocolytic
• ISSN: 0312-5963; 1179-1926; 1179-1926
• 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 (AUC ss ) 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.