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Pharmacokinetics of Indomethacin in Pregnancy

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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.

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Acknowledgments

This work was supported by grant U10HD047891 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Obstetrical Pharmacology Research Units Network (OPRU), to G.D.V. Hankins. The authors sincerely appreciate the support of the physicians and nurses of the Labor and Delivery Ward at John Sealy Hospital, the teaching hospital at the University of Texas Medical Branch, Galveston, Texas, nursing coordinator Aimee Jackson, and the Perinatal Research Division of the Department of Obstetrics and Gynecology. Dawn Fischer, RN, from the Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, is also thanked for her assistance. Erik Rytting, Tatiana N. Nanovskaya, Xiaoming Wang, Daria I. Vernikovskaya, Shannon M. Clark, Marlo Cochran, Susan M. Abdel-Rahman, Raman Venkataramanan, Steve N. Caritis, Gary D.V. Hankins, and Mahmoud S. Ahmed have no conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0587, USA

    Erik Rytting, Tatiana N. Nanovskaya, Xiaoming Wang, Daria I. Vernikovskaya, Shannon M. Clark, Marlo Cochran, Gary D. V. Hankins & Mahmoud S. Ahmed

  2. Children’s Mercy Hospital, Kansas City, MO, USA

    Susan M. Abdel-Rahman

  3. Departments of Pharmaceutical Sciences and Pathology, University of Pittsburgh, Pittsburgh, PA, USA

    Raman Venkataramanan

  4. Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, PA, USA

    Steve N. Caritis

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  1. Erik Rytting
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  2. Tatiana N. Nanovskaya
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  3. Xiaoming Wang
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  4. Daria I. Vernikovskaya
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  5. Shannon M. Clark
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  7. Susan M. Abdel-Rahman
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  9. Steve N. Caritis
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  11. Mahmoud S. Ahmed
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Corresponding author

Correspondence to Erik Rytting.

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Rytting, E., Nanovskaya, T.N., Wang, X. et al. Pharmacokinetics of Indomethacin in Pregnancy. Clin Pharmacokinet 53, 545–551 (2014). https://doi.org/10.1007/s40262-014-0133-6

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