Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet - A randomized, controlled trial
Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet - A randomized, controlled trial
复制标题
DOI：
10.7326/0003-4819-133-1-200007040-00002
复制
发表时间：
2000-07-04
影响因子：
39.2
通讯作者：
Yao, SL
中科院分区：
文献类型：
--
作者：
Swan, SK;Rudy, DW;Yao, SL
背景：大多数非甾体抗炎药（NSAIDs）既抑制环氧化酶-1 (COX-1)，其抑制与胃肠道溃疡有关，又抑制COX-2，其抑制与治疗益处有关。虽然不产生COX-1活性的药物可能副作用较小，但在小鼠中靶向破坏COX-2等位基因会导致严重的肾脏问题，这表明抑制COX-2也可能产生副作用。目的：探讨coxib类药物罗非昔布对老年患者肾功能的影响。罗非昔布是COX-2酶特异性抑制剂。设计：一项随机、三期、单剂量交叉研究和一项随机、平行组、多剂量研究。单位：临床研究单位。患者：60 ~ 80岁患者75例。干预措施：在第一项研究中，单剂量罗非昔布，250 mg（约为推荐剂量的1 - 20倍）；吲哚美辛，75毫克；15名患者服用安慰剂。在第二项研究中，多剂量的罗非昔布，12.5或25mg /d；吲哚美辛，50毫克，每日3次；60名患者服用安慰剂。两项研究中的患者均接受低钠饮食测量：肾小球滤过率、肌酐清除率、尿和血清钠和钾值。结果：与安慰剂相比，单剂量罗非昔布和吲哚美辛分别使肾小球滤过率降低0.23 mL/s （P < 0.001）和0.18 mL/s （P = 0.003）。多剂量12.5 mg/d的罗非昔布分别降低0.14、0.13、0.10 mL/s (P = 0.019)；给予罗非昔布25 mg （P = 0.029）和吲哚美辛（P = 0.086）。肌酐清除率、血清和尿钠、钾的变化不太明显。结论：COX-2抑制对肾功能的影响与非选择性非甾体抗炎药相似。因此，COX-2似乎在人体肾功能中起着重要作用。
Background: Most nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both cyclooxygenase-1 (COX-1), whose inhibition is associated with gastrointestinal ulceration, and COX-2, whose inhibition is associated with therapeutic benefits. Although agents that do not produce COX-1 activity may have fewer adverse effects, targeted disruption of the COX-2 allele in mice has resulted in severe renal problems, suggesting that COX-2 inhibition may also produce adverse effects.Objective: To determine the effect of rofecoxib, a member of the coxib class of drugs and a specific inhibitor of the COX-2 enzyme, on renal function in elderly patients.Design: A randomized, three-period, single-dose crossover study and a randomized, parallel-group, multiple-dose study.Setting: Clinical research units.Patients: 75 patients 60 to 80 years of age.Intervention: In the first study, single doses of rofecoxib, 250 mg (about Ei-fold to 20-fold the recommended dose); indomethacin, 75 mg; and placebo were administered to 15 patients. In the second study, multiple doses of rofecoxib, 12.5 or 25 mg/d; indomethacin, 50 mg three times daily; or placebo were administered to 60 patients. Patients in both studies received a low-sodium dietMeasurements: Glomerular filtration rate, creatinine clearance, and urinary and serum sodium and potassium values.Results: Compared with placebo, single doses of rofecoxib and indomethacin decreased the glomerular filtration rate by 0.23 mL/s (P < 0.001) and 0.18 mL/s (P = 0.003), respectively. In contrast, respective decreases of 0.14, 0.13, and 0.10 mL/s were observed after multiple doses of rofecoxib, 12.5 mg/d (P = 0.019); rofecoxib, 25 mg (P = 0.029), and indomethacin (P = 0.086) were administered. Changes in creatinine clearance and serum and urinary sodium and potassium were less pronounced.Conclusions: The effects of COX-2 inhibition on renal function are similar to those observed with nonselective NSAIDs. Thus, COX-2 seems to play an important role in human renal function.