Laine L, Sloane R, Ferretti M, Cominelli F
Division of Gastrointestinal and Liver Diseases, University of Southern California School of Medicine, Los Angeles, USA.
Gastrointest Endosc. 1995 Nov;42(5):428-33. doi: 10.1016/s0016-5107(95)70045-5.
NSAIDs frequently cause gastrointestinal injury and increase the risk of ulcer complications. We compared an NSAID suggested to cause less gastric injury (etodolac) with a standard NSAID (naproxen) and a placebo in a 4-week double-blind trial assessing the effects on gastroduodenal injury, symptoms, and prostaglandin production in healthy volunteers.
Fifty-two healthy volunteers not taking NSAIDs, alcohol, antibiotics, bismuth, or anti-ulcer drugs: placebo, etodolac 400 mg, or naproxen 500 mg b.i.d. for 4 weeks. Endoscopies with biopsies were repeated at weeks 1 and 4. The number and dimensions of ulcers and erosions were recorded to quantitate injury.
At week 1 the mean number and area of gastric ulcers per subject were greater with naproxen than placebo or etodolac (area: naproxen, 7.4 mm2; placebo, 0.6 mm2, p = 0.02 vs naproxen; etodolac, 2.1 mm2, p = 0.06 vs naproxen). Ulcer scores at week 4 were low and comparable in the three groups. The mean number and area of gastric erosions per subject were greatest with naproxen at both weeks 1 and 4 (week 4 area: naproxen, 58.3 mm2; placebo, 29.0 mm2; etodolac, 13.9 mm2, p < 0.02, naproxen vs placebo and vs etodolac). Placebo injury was presumably due to biopsies at prior endoscopy. Gastric mucosal prostaglandin E2 production did not change significantly from baseline after 1 or 4 weeks of treatment with placebo or etodolac, but did decrease significantly with naproxen (week 0, 1689; week 1, 479; week 4, 577 pg/mg protein). Gastrointestinal symptoms were present in only 1 (5%) of 20 visits in which endoscopy showed no erosions or ulcers vs 21 (26%) of 82 visits in which a mucosal defect was identified (p = 0.666).
Gastric injury with 4 weeks of etodolac is comparable to that seen with placebo and significantly less than that occurring with naproxen, presumably due to the fact that etodolac does not suppress gastric mucosal prostaglandin production, whereas naproxen leads to a significant reduction.
非甾体抗炎药（NSAIDs）常导致胃肠道损伤并增加溃疡并发症风险。在一项为期4周的双盲试验中，我们比较了一种据称胃损伤较小的NSAID（依托度酸）与标准NSAID（萘普生）及安慰剂对健康志愿者胃十二指肠损伤、症状和前列腺素生成的影响。
52名未服用NSAIDs、酒精、抗生素、铋剂或抗溃疡药物的健康志愿者：服用安慰剂、400 mg依托度酸或500 mg萘普生，每日2次，共4周。在第1周和第4周重复进行内镜检查及活检。记录溃疡和糜烂的数量及大小以量化损伤程度。
在第1周，服用萘普生的受试者胃溃疡的平均数量和面积大于服用安慰剂或依托度酸的受试者（面积：萘普生7.4 mm²；安慰剂0.6 mm²，与萘普生相比p = 0.02；依托度酸2.1 mm²，与萘普生相比p = 0.06）。第4周时溃疡评分较低，三组相当。在第1周和第4周，服用萘普生的受试者胃糜烂的平均数量和面积均最大（第4周面积：萘普生58.3 mm²；安慰剂29.0 mm²；依托度酸13.9 mm²，萘普生与安慰剂及依托度酸相比p < 0.02）。安慰剂组的损伤可能是由于之前内镜检查时的活检所致。服用安慰剂或依托度酸治疗1周或4周后，胃黏膜前列腺素E2生成与基线相比无显著变化，但服用萘普生后显著降低（第0周1689；第1周479；第4周577 pg/mg蛋白）。在内镜检查未发现糜烂或溃疡的20次就诊中，仅1次（5%）出现胃肠道症状，而在发现黏膜缺损的82次就诊中有21次（26%）出现胃肠道症状（p = 0.666）。
服用4周依托度酸后的胃损伤与服用安慰剂相当，且明显小于服用萘普生后的损伤，这可能是因为依托度酸不抑制胃黏膜前列腺素生成，而萘普生会导致其显著减少。
