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依托度酸,一种新型非甾体抗炎药:胃肠道微出血及内镜研究

Etodolac, a new nonsteroidal anti-inflammatory drug: gastrointestinal microbleeding and endoscopic studies.

作者信息

Lanza F L, Arnold J D

出版信息

Clin Rheumatol. 1989 Mar;8 Suppl 1:5-15. doi: 10.1007/BF02214105.

Abstract

A review of the literature is presented on the gastrointestinal effects of etodolac, a new nonsteroidal anti-inflammatory drug (NSAID), as evaluated in both microbleeding and endoscopic studies. In four microbleeding studies, gastrointestinal blood loss in healthy subjects was estimated by a 51Cr-erythrocyte labeling method before drug treatment, after 7 days of treatment with NSAIDs including etodolac, and 1 week after the last day of treatment. In these 7-day studies, the gastrointestinal blood loss seen with etodolac (600 to 1200 mg/day) was similar to that seen with placebo and significantly (p less than 0.05) less than that seen with aspirin (2600 mg/day), naproxen (750 mg/day), ibuprofen (2400 mg/day), or indomethacin (200 mg/day). Naproxen, ibuprofen, and indomethacin caused mean daily blood losses in excess of 1 ml/day over baseline values. The increase with aspirin was 4 to 5 ml/day. In contrast, the greatest mean daily increase in blood loss with etodolac therapy was 0.2 ml. In a 4-week study of etodolac (600 and 1000 mg/day) and piroxicam (20 mg/day) given to patients with osteoarthritis or rheumatoid arthritis, blood loss seen with etodolac was comparable to that seen with placebo and significantly less than that seen with piroxicam. Gastrointestinal irritation was also assessed by endoscopy after 1 week of NSAID or placebo treatment. Endoscopy scores after etodolac treatment (up to 1200 mg/day) were similar to scores at baseline and after placebo and were significantly lower than scores following treatment with aspirin (3900 mg/day), indomethacin (200 mg/day), ibuprofen (2400 mg/day), or naproxen (100 mg/day). The effects of etodolac (600 or 1000 mg/day) and diclofenac (150 mg/day) were not different from each other or from baseline. These data indicate that etodolac, in these studies, did not cause clinically significant gastrointestinal microbleeding or visible gastric injury. By the criteria used in these studies, etodolac is less irritating to the gastrointestinal tract than aspirin, indomethacin, ibuprofen, naproxen, or piroxicam, and compares favorably with diclofenac.

摘要

本文综述了新型非甾体抗炎药依托度酸对胃肠道的影响,这些影响是在微量出血和内镜研究中评估得出的。在四项微量出血研究中,通过51Cr红细胞标记法在药物治疗前、使用包括依托度酸在内的非甾体抗炎药治疗7天后以及治疗最后一天后1周,对健康受试者的胃肠道失血情况进行了估计。在这些为期7天的研究中,依托度酸(600至1200毫克/天)导致的胃肠道失血与安慰剂相似,且显著低于阿司匹林(2600毫克/天)、萘普生(750毫克/天)、布洛芬(2400毫克/天)或吲哚美辛(200毫克/天)(p小于0.05)。萘普生、布洛芬和吲哚美辛导致的平均每日失血量超过基线值1毫升/天。阿司匹林导致的失血量增加为4至5毫升/天。相比之下,依托度酸治疗导致的最大平均每日失血量增加为0.2毫升。在一项针对骨关节炎或类风湿关节炎患者进行的为期4周的研究中,给予依托度酸(600和1000毫克/天)和吡罗昔康(20毫克/天),依托度酸导致的失血与安慰剂相当,且显著低于吡罗昔康。在非甾体抗炎药或安慰剂治疗1周后,还通过内镜检查评估了胃肠道刺激情况。依托度酸治疗(剂量高达1200毫克/天)后的内镜检查评分与基线及安慰剂后的评分相似,且显著低于阿司匹林(3900毫克/天)、吲哚美辛(200毫克/天)、布洛芬(2400毫克/天)或萘普生(100毫克/天)治疗后的评分。依托度酸(600或1000毫克/天)与双氯芬酸(150毫克/天)的效果彼此之间以及与基线相比并无差异。这些数据表明,在这些研究中,依托度酸未引起具有临床意义的胃肠道微量出血或可见的胃损伤。根据这些研究中使用的标准,依托度酸对胃肠道的刺激性低于阿司匹林、吲哚美辛、布洛芬、萘普生或吡罗昔康,且与双氯芬酸相比具有优势。

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