Clària Joan, Kent Jeffrey D, López-Parra Marta, Escolar Ginés, Ruiz-Del-Arbol Luís, Ginès Pere, Jiménez Wladimiro, Vucelic Boris, Arroyo Vicente
DNA Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Hepatology. 2005 Mar;41(3):579-87. doi: 10.1002/hep.20595.
Nonselective inhibition of cyclooxygenase (COX) by nonsteroidal anti-inflammatory drugs frequently induces renal failure in decompensated cirrhosis. Studies in experimental cirrhosis suggest that selective inhibitors of the inducible isoform COX-2 do not adversely affect renal function. However, very limited information is available on the effects of these compounds on renal function in human cirrhosis. This investigation consists of a double-blind, randomized, placebo-controlled trial aimed at comparing the effects of the selective COX-2 inhibitor celecoxib (200 mg every 12 hours for a total of 5 doses) on platelet and renal function and the renal response to furosemide (40 mg intravenously) with those of naproxen (500 mg every 12 hours for a total of 5 doses) and placebo in 28 patients with cirrhosis and ascites. A significant reduction (P < .05) in glomerular filtration rate (113 +/- 27 to 84 +/- 22 mL/min), renal plasma flow (592 +/- 158 to 429 +/- 106 mL/min) and urinary prostaglandin E(2) excretion (3430 +/- 430 to 2068 +/- 549 pg/min) and suppression of the diuretic (urine volume: 561 +/- 128 to 414 +/- 107 mL/h) and natriuretic (urine sodium: 53 +/- 13 to 34 +/- 10 mEq/h) responses to furosemide were observed in the group of patients treated with naproxen but not in the other two groups. Naproxen, but not celecoxib or placebo, significantly inhibited platelet aggregation (72% +/- 8% to 47% +/- 8%, P < .05) and thromboxane B(2) production (41 +/- 12 to 14 +/- 5 pg/mL, P < .05). In conclusion, our results indicate that short-term administration of celecoxib does not impair platelet and renal function and the response to diuretics in decompensated cirrhosis. Further studies are needed to evaluate the long-term safety of this drug in cirrhosis.
非甾体抗炎药对环氧化酶（COX）的非选择性抑制作用常导致失代偿期肝硬化患者出现肾衰竭。实验性肝硬化研究表明，诱导型同工酶COX - 2的选择性抑制剂不会对肾功能产生不利影响。然而，关于这些化合物对人类肝硬化患者肾功能影响的信息非常有限。本研究为一项双盲、随机、安慰剂对照试验，旨在比较选择性COX - 2抑制剂塞来昔布（每12小时200毫克，共5剂）与萘普生（每12小时500毫克，共5剂）及安慰剂对28例肝硬化腹水患者血小板功能、肾功能以及对呋塞米（静脉注射40毫克）的肾脏反应的影响。萘普生治疗组患者的肾小球滤过率（从113±27降至84±22毫升/分钟）、肾血浆流量（从592±158降至429±106毫升/分钟）、尿前列腺素E2排泄量（从3430±430降至2068±549皮克/分钟）显著降低（P <.05），对呋塞米的利尿反应（尿量：从561±128降至414±107毫升/小时）和利钠反应（尿钠：从53±13降至34±10毫当量/小时）受到抑制，而其他两组未出现此现象。萘普生而非塞来昔布或安慰剂能显著抑制血小板聚集（从72%±8%降至47%±8%，P <.05）和血栓素B2生成（从41±12降至14±5皮克/毫升，P <.05）。总之，我们的结果表明，短期服用塞来昔布不会损害失代偿期肝硬化患者的血小板功能、肾功能及对利尿剂的反应。需要进一步研究评估该药物在肝硬化患者中的长期安全性。
