Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0587, USA,
Clin Pharmacokinet. 2014 Jun;53(6):545-51. doi: 10.1007/s40262-014-0133-6.
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.
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.
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.
Further studies are needed to determine whether any dose adjustments are necessary as a result of the increased clearance of indomethacin during pregnancy.
尽管吲哚美辛在过去 40 年中被广泛用于治疗早产，但关于其在孕妇中的药代动力学的报道很少。
本研究为机会性研究，评估了每天口服 25mg 吲哚美辛 6 小时的孕妇的稳态药代动力学。采用经验证的高效液相色谱-质谱联用方法分析血浆和尿液中的吲哚美辛浓度。
稳态时的平均血浆浓度-时间曲线下面积（AUCss）为 1.91±0.53μg·h/mL，平均峰血浆浓度（C max）为 1.02±0.49μg/mL，达到 C max的平均时间（t max）为 1.3±0.7h。稳态时的平均表观清除率为 14.5±5.5L/h，高于文献报道的非孕妇的表观清除率。吲哚美辛可穿过胎盘；5 份分娩时采集的脐血样本的平均胎儿/母体比值为 4.0±1.1。
需要进一步研究以确定是否需要因妊娠期间吲哚美辛清除率增加而调整剂量。
