Brash A R, Hickey D E, Graham T P, Stahlman M T, Oates J A, Cotton R B
N Engl J Med. 1981 Jul 9;305(2):67-72. doi: 10.1056/NEJM198107093050203.
To identify factors affecting the efficacy of indomethacin in closing symptomatic patent ductus arteriosus (PDA), we studied the pharmacokinetics of intravenous indomethacin, 0.2 mg per kilogram of body weight, in 35 premature infants with symptomatic PDA. Most infants responded to indomethacin with ductus constriction. Indomethacin infusions that were ineffective (seven doses in six patients) were associated with significantly faster clearance, a shorter half-life, and lower plasma levels (p less than 0.05). Six infants had later reopening of the ductus. All six received indomethacin in the first postnatal week; they could not be distinguished from infants with permanent closure on the basis of indomethacin kinetics, but they were of low gestational age. There was a 20-fold variation in plasma indomethacin levels 24 hours after a dose. In view of this variation and the relation between plasma levels and ductus constriction, we suggest that measurement of the plasma indomethacin level could be of value in infants with no response to a first dose.
为了确定影响吲哚美辛关闭有症状动脉导管未闭（PDA）疗效的因素，我们研究了35例有症状PDA早产儿静脉注射每千克体重0.2毫克吲哚美辛的药代动力学。大多数婴儿对吲哚美辛有动脉导管收缩反应。无效的吲哚美辛输注（6例患者7剂）与清除率显著加快、半衰期缩短和血浆水平降低有关（p<0.05）。6例婴儿动脉导管后来重新开放。所有6例均在出生后第一周接受了吲哚美辛治疗；根据吲哚美辛动力学，他们与动脉导管永久关闭的婴儿无法区分，但他们的胎龄较小。给药后24小时血浆吲哚美辛水平有20倍的差异。鉴于这种差异以及血浆水平与动脉导管收缩之间的关系，我们建议对首剂无反应的婴儿测量血浆吲哚美辛水平可能有价值。
