Chamaa N S, Mosig D, Drukker A, Guignard J P
Division of Pediatric Nephrology and Department of Pediatrics, University Medical Center, Lausanne, Switzerland.
Pediatr Res. 2000 Nov;48(5):600-5. doi: 10.1203/00006450-200011000-00008.
In early childhood, nonsteroidal anti-inflammatory drugs are mainly used to either prevent or treat premature labor of the mother and patent ductus arteriosus of the newborn infant. The most frequently used prostaglandin-synthesis inhibitor is indomethacin. Fetuses exposed to indomethacin in utero have been born with renal developmental defects, and in both the unborn child and the term and premature newborn this drug may compromise renal glomerular function. The latter has in the past also been observed when i.v. indomethacin or i.v. acetylsalicylic acid (aspirin) were administered to newborn rabbits. The present experiments were designed to evaluate whether ibuprofen has less renal side effects than indomethacin, as claimed. Three groups of anesthetized, ventilated, normoxemic neonatal rabbits were infused with increasing doses of ibuprofen (0.02, 0.2, 2.0 mg/kg body weight) and the following renal parameters were measured: urine volume, urinary sodium excretion, GFR, and renal plasma flow. Renal blood flow, filtration fraction, and the renal vascular resistance were calculated according to standard formulae. Intravenous ibuprofen caused a dose-dependent, significant reduction in urine volume, GFR, and renal blood flow with a fall in filtration fraction in the animals receiving the highest dose of ibuprofen (2 mg/kg body weight). There was a very steep rise in renal vascular resistance. Urinary sodium excretion decreased. These experiments in neonatal rabbits clearly show that acute i.v. doses of ibuprofen also have significant renal hemodynamic and functional side effects, not less than seen previously with indomethacin.
在幼儿期，非甾体抗炎药主要用于预防或治疗母亲的早产以及新生儿的动脉导管未闭。最常用的前列腺素合成抑制剂是吲哚美辛。在子宫内接触吲哚美辛的胎儿出生时伴有肾脏发育缺陷，并且对于未出生的胎儿以及足月儿和早产儿，这种药物可能会损害肾小球功能。过去在给新生兔静脉注射吲哚美辛或静脉注射乙酰水杨酸（阿司匹林）时也观察到了后者的情况。本实验旨在评估布洛芬是否如所声称的那样比吲哚美辛具有更少的肾脏副作用。将三组麻醉、通气、血氧正常的新生兔输注递增剂量的布洛芬（0.02、0.2、2.0毫克/千克体重），并测量以下肾脏参数：尿量、尿钠排泄、肾小球滤过率（GFR）和肾血浆流量。根据标准公式计算肾血流量、滤过分数和肾血管阻力。静脉注射布洛芬导致尿量、GFR和肾血流量呈剂量依赖性显著降低，在接受最高剂量布洛芬（2毫克/千克体重）的动物中滤过分数下降。肾血管阻力急剧上升。尿钠排泄减少。这些新生兔实验清楚地表明，静脉注射急性剂量的布洛芬也具有显著的肾脏血流动力学和功能副作用，并不比先前使用吲哚美辛时少。
