Winther J B, Hoskins E, Printz M P, Mendoza S A, Kirkpatrick S E, Friedman W F
Biol Neonate. 1980;38(1-2):76-84. doi: 10.1159/000241343.
Transient renal dysfunction has been observed in some premature infants who received indomethacin to constrict patent ductus arteriosi, and it has been suggested that this complication may be dose related. Accordingly, the present study was designed to investigate the influence of high (7.5 mg/kg) and low (0.2 mg/kg) doses of indomethacin on effective renal blood flow, glomerular filtration rate, urine flow, sodium and potassium excretion and plasma levels of indomethacin in conscious newborn lambs studied continously over a 24-hour period. When compared to control lambs, both indomethacin doses reduced effective renal blood flow significantly at 2--4 h, but only high doses significantly reduced renal blood flow at 22--24 h (6.5 +/- 0.9 vs. 13.4 +/- 1.4 ml/min/kg, respectively; p less than 0.001). At 8-16 and 16-24 h after drug administration, urine flow was significantly lower than in the control group only in high-dose lambs (p less than 0.05). During the 16 to 24-hour period, urine flow for control, low- and high-dose animals was 0.15 +/- 0.01, 0.14 +/- 0.01, and 0.08 +/- 0.02 ml/min/kg, respectively. Glomerular filtration rate and sodium and potassium excretion rates were not affected by either indomethacin dose.
在一些接受吲哚美辛以收缩动脉导管未闭的早产儿中观察到短暂性肾功能障碍，有人提出这种并发症可能与剂量有关。因此，本研究旨在调查高剂量（7.5毫克/千克）和低剂量（0.2毫克/千克）吲哚美辛对清醒新生羔羊有效肾血流量、肾小球滤过率、尿流量、钠和钾排泄以及吲哚美辛血浆水平的影响，这些羔羊在24小时内持续接受研究。与对照羔羊相比，两种剂量的吲哚美辛在2至4小时时均显著降低了有效肾血流量，但只有高剂量在22至24小时时显著降低了肾血流量（分别为6.5±0.9与13.4±1.4毫升/分钟/千克；p<0.001）。在给药后8至16小时和16至24小时，仅高剂量组羔羊的尿流量显著低于对照组（p<0.05）。在16至24小时期间，对照、低剂量和高剂量动物的尿流量分别为0.15±0.01、0.14±0.01和0.08±0.02毫升/分钟/千克。两种剂量的吲哚美辛均未影响肾小球滤过率以及钠和钾的排泄率。
