N14对正常大鼠消化道致溃疡作用

目的 观察N14是否有致胃肠溃崭作用。方法 对正常大鼠进行连续ig给药7 d．1次·d^-t并与阿斯匹林、吲哚美辛进行对照．剂量分别为N14，25，50，100mg·kg^-1，阿斯匹林25，50．100mg·kg^-1，吲哚美辛1．25，2．5,5mg·kg^-1．结果 N14组与溶媒对照组的结果相近．各大鼠均无明显胃肠溃疡发生，阿斯匹林有明显致胃溃痔作用(P<0．05)，吲哚美辛有非常明显的致胃溃汤作用(P<0.01)．结论N14对胃肠遭无致溃汤作用，为进一步研究该药提供实验数据．     

瓦松提取物对实验性胃溃疡的治疗作用

目的：观察瓦松提取物对实验性胃溃疡的治疗作用。方法：以Wistar大鼠和昆明种小鼠为研究对象,复制5种实验性胃溃疡动物模型（小鼠束缚水浸应激致胃溃疡模型、吲哚美辛致小鼠胃溃疡模型、乙醇致大鼠胃溃疡模型、乙酸致大鼠胃溃疡模型和大鼠幽门结扎致胃溃疡模型）。将大鼠随机分为瓦松提取物400、200、100mg/kg剂量组、阳性对照组和模型对照组;小鼠随机分成瓦松提取物800、400、200mg/kg剂量组、阳性对照组和模型对照组。测定胃溃疡指数、胃液游离酸排出量及总酸排出量。结果：瓦松提取物400、800mg/kg剂量组能降低小鼠应激性溃疡溃疡指数（P〈0.05）;200～800mg/kg瓦松提取物对吲哚美辛致小鼠胃溃疡溃疡指数有明显的降低作用（P〈0.05或P〈0.01）;同时对乙醇引起的大鼠胃溃疡也具有明显的抑制作用（P〈0.05）,并可明显促进乙酸致大鼠胃溃疡溃疡的愈合,但对动物胃液分泌及胃蛋白酶活性无明显影响。结论：瓦松提取物对实验性胃溃疡有明显的预防和治疗作用。     

谷氨酰胺对非甾体抗炎药所致大鼠小肠黏膜损伤预防作用的研究

目的:研究谷氨酰胺对非甾体抗交药(NSAIDs)所致大鼠小肠黏膜损伤的预防作用,为临床安全用药提供依据.方法:清洁级雄性SD大鼠90只,随机分为9组:4个模型组、4个预防组及1个空白对照组,每组10只.4个模型组分别给予吲哚美辛2.5 mg/kg、阿司匹林50 mg/kg、布洛芬30 mg/kg或塞来昔布20 mg/kg每天2次连续14 d;4个预防组大鼠在给予上述不同NSAIDs的同时给予L-谷氨酰胺100 mg/kg,药物均溶于0.5%羧甲基纤维素钠(CMC)2 ml中灌胃;空白对照组大鼠仅给予CMC 2 ml.第15天处死大鼠,采用CMIAS多功能真彩色图像分析系统测量每只大鼠小肠黏膜损伤深度、面积,计算累计损伤深度和累计面积;并应用检测试剂盒测定小肠组织匀浆中髓过氧化物酶(MPO)、丙二醛(MDA)、超氧化物歧化酶(SOD)和一氧化氮(NO)含量.结果:吲哚美辛、阿司匹林、布洛芬及塞来昔布模型组小肠黏膜累计损伤深度分别为5954、511、1361和1447μm,累计损伤面积分别为1 956 592、164 304、339 711和445 611 μm2,除阿司匹林组外,其余各组与空白对照组比较差异均有统计学意义(均P<0.05).吲哚美辛模型组损伤程度重于其他各组(均P<0.05).吲哚美辛、阿司匹林、布洛芬和塞来昔布预防组小肠黏膜损伤累计深度和面积分别为1206.443、616.723 μm和390 450、92 192、209 655、238 827 μm2,损伤程度均明显低于对应模型组.吲哚美辛、阿司匹林、布洛芬和塞来昔布各预防组MPO分别为(1.10±0.35)、(0.53±0.19)、(0.83±0.24)和(0.37±0.17)U/g,各对应模型组MPO分别为(2.37±0.63)、(1.66±0.50)、(1.35±0.35)和(1.14±0.38)U/g.各预防组的MPO明显低于各对应模型组,差异有统计学意义,均P<0.05.吲哚美辛预防组MDA明显低于吲哚美辛模型组[(0.50±0.16)比(1.19±0.77)nmol/mg,P<0.05)].吲哚美辛、阿司匹林、布洛芬和塞来昔布模型组SOD分别为(3.53±0.64)、(4.03±1.28)、(3.44±1.05)和(3.70±1.53)U/mg,均明显低于空白对照组[(5.49±1.09)U/mg,均P<0.05)],各对应预防组SOD分别为(4.03±1.28)、(4.46±1.53)、(4.29±1.10)和(4.00±1.08)U/mg,高于各模型组,但差异无统计学意义.各预防组与各模型组间NO水平差异无统计学意义(P>0.05).结论:谷氨酰胺对4种NSAIDs所致大鼠小肠黏膜损伤具有预防作用.     

茅苍术水提物体外对大鼠实验性胃溃疡的影响

目的:研究茅苍术水提物体外对大鼠实验性胃溃疡的影响。方法:采用SD大鼠为研究对象和无水乙醇体外致大鼠胃溃疡为模型;将大鼠随机分为茅苍术水提物0.8 g/kg剂量组和4 g/kg剂量组、正常对照组、胃舒平(阳性药)组和模型组;测定胃溃疡指数、胃液总酸排出量和胃蛋白酶的活性,分析各指标的变化情况。结果:茅苍术水提物对无水乙醇性胃溃疡大鼠,能够明显降低胃蛋白酶的活性(P<0.05),促进溃疡愈合,但其对胃液总酸度无明显影响;茅苍术水提物4 g/kg剂量组缩小溃疡面积优于0.8 g/kg剂量组和其他各组(P<0.05)。结论:茅苍术水提物体外对实验性胃溃疡大鼠具有一定的预防和保护作用。     

氯波必利生物黏附型缓释片对实验性胃溃疡和胃肠动力障碍的作用研究

目的:研究氯波必利(CBP)生物黏附型缓释片对实验性胃溃疡和胃肠动力障碍的作用。方法:取大鼠以乙醇+阿司匹林法复制胃溃疡模型后,分为模型(生理盐水)组、普通片(CBP片0.072 mg/kg)组和缓释片高、低剂量(CBP生物黏附型缓释片0.072、0.036 mg/kg)组,另取正常大鼠为正常对照(生理盐水)组;除缓释片组每日ig药物2次外,其余组每日给药3次,给药第2、4天后解剖观察溃疡面积,计算溃疡愈合率(n=6)。取小鼠以阿托品复制胃肠动力障碍模型后,分为模型(生理盐水)组、普通片(CBP片0.1 mg/kg)组和缓释片高、中、低剂量(CBP生物黏附型缓释片0.1、0.05、0.025 mg/kg)组,另取正常小鼠为正常对照(生理盐水)组,每日ig药物1次,连续3 d,检测小鼠胃排空率和小肠推进率(n=6)。结果:与正常对照组比较,模型组大鼠溃疡面积增加;与模型组比较,普通片组和缓释片高、低剂量组大鼠溃疡面积减小,差异有统计学意义(P<0.01),给药2 d的愈合率为32.35%~48.24%,给药4 d的愈合率均超过70%。与正常对照组比较,模型组小鼠胃排空率和小肠推进率降低;与模型组比较,普通片组和缓释片高、中、低剂量组小鼠胃排空率和小肠推进率升高,其中缓释片高、中剂量组作用效果强于普通片组,以上差异均有统计学意义(P<0.01或P<0.05)。结论:CBP生物黏附型缓释片对大鼠胃溃疡和小鼠胃肠动力障碍均有改善作用。     

注射用雷贝拉唑钠对不同溃疡模型大鼠的影响

目的 比较注射用雷贝拉唑钠对不同溃疡模型大鼠的影响。方法 采用幽门结扎法收集胃液,测定注射用雷贝拉唑钠0.5、1.0、2.0、4.0、8.0 mg/kg对大鼠胃液酸度、胃酸总分泌量的影响。制备吲哚美辛引起的胃溃疡模型、醋酸性胃溃疡、大鼠反流性食管炎以及半胱胺型十二指肠溃疡,模型动物iv给予注射用雷贝拉唑钠后,对溃疡进行评分,计算溃疡抑制情况。结果 ①与模型组比较,注射用雷贝拉唑钠8 mg/kg组胃液分泌量,0.5、4.0、8.0 mg/kg组胃液酸度,2、4、8 mg/kg剂量组胃酸分泌量均显著降低（P<0.05、0.01）。②与模型组比较,0.5、1.0、2.0、4.0 mg/kg剂量组吲哚美辛引起的溃疡得分均显著降低（P<0.05、0.01）。③注射用雷贝拉唑钠1 mg/kg对大鼠醋酸性胃溃疡、反流性食管炎、半胱胺型十二指肠溃疡抑制率分别为18.2%、37.5%和23.4%,其中对反流性食管炎的抑制作用具有显著性差异（P<0.05）。结论 注射用雷贝拉唑钠抑制胃酸分泌,对吲哚美辛引起胃溃疡、反流性食管炎、十二指肠溃疡和醋酸性胃溃疡均有抑制作用。     

谓葆对胃炎及胃溃疡作用的研究

目的观察谓葆抗实验性胃炎、胃溃疡及止痛镇痛的作用。方法采用大鼠无水乙醇胃炎模型、消炎痛胃溃疡模型、幽门结扎溃疡模型以及慢性醋酸型溃疡模型,观察谓葆的抗胃炎及抗胃溃疡作用,并采用小鼠醋酸扭体试验方法对其止痛镇痛作用进行观察。结果谓葆低中高剂量(75mg/kg、150mg/kg和300mg/kg)均减少大鼠无水乙醇模型的胃黏膜损伤面积(与对照组相比P<0.05);降低大鼠消炎痛胃溃疡模型的损伤指数(P<0.05)及大鼠幽门结扎溃疡模型的溃疡指数(P<0.05);对大鼠慢性醋酸型溃疡模型也有良好的保护作用,给药组溃疡体积较对照组减少(P<0.05)。谓葆两个剂量(75mg/kg和150mg/kg)均降低醋酸扭体试验小鼠的扭体次数(P<0.05)。结论谓葆具有抗多种胃炎和胃溃疡作用,并有止痛镇痛作用。     

娑罗子提取物对阿司匹林致胃溃疡作用的研究

目的研究娑罗子提取物（SAE）对阿司匹林所致胃溃疡的保护作用,为阿司匹林安全用药提供依据。方法用阿司匹林制备溃疡模型,小鼠连续5天灌胃给予SAE（3.5、7、14mg/kg）或在制备溃疡模型前、后不同时间点灌胃给予SAE（7mg/kg）,于显微镜下观察胃溃疡指数。结果与模型组比较,SAE（7、14mg/kg）显著降低溃疡指数（P〈0.05）。制备溃疡模型同时给予SAE（7mg/kg）可以明显降低溃疡指数。结论娑罗子提取物对阿司匹林所致胃溃疡有预防作用。     

伊索拉定的药理和临床研究

伊索拉定(irsogladine,商品名:Gaslon)是胃粘膜保护剂,由日本新药株式会社中央研究所研制,1989年在日本上市。由于该药对胃炎、胃溃疡具有较好的疗效,服用方便,副作用少。因此,在国外日益受到重视。本文对其药理作用、临床应用及不良反应等作一综述。1　药理作用1.1　药效学　1抗溃疡作用　该药对水浸应激性溃疡(大鼠)、乙醇溃疡(大鼠)、阿司匹林溃疡(大鼠)、急性实验溃疡及醋酸胃溃疡(大鼠)、电溃疡(狗)、以及慢性实验溃疡,在1～10mg/kg低剂量时仍显示有抗溃疡作用[1,2]。2抗胃炎作用　对应力胃粘膜损伤性胃炎,0.1～1mg/kg剂量下,具有愈合…     

吲哚拉新(Indolacin)的药理研究

吲哚拉新灌胃给药,对角叉菜胶所致大鼠踝关节肿胀具有抑制作用,其 ED_(50)为11.6±6.0mg/kg,对醋酸所致小鼠扭体反应具有抑制作用,其 ED_(50)为111.7±18.1mg/kg。吲哚拉新腹腔注射30mg/kg,对四联菌苗所致家兔体温升高具有降低作用。吲哚拉新灌胃给药80mg/kg 和100mg/kg,对部分大鼠有致胃溃疡作用;同时灌胃给予白芨—甘草和角叉菜胶,剂量均为1600mg/kg,均有抗吲哚拉新致胃溃疡作用。     

Inhibition by aspirin of gastrointestinal toxicity induced by indomethacin in polyarthritic rats.

Methods were employed for examining the gastrointestinal toxicity of indomethacin, aspirin, and combinations of these drugs in adjuvant-induced polyarthritic rats. Significant toxicity, primarily associated with the small intestine, was observed at doses between 4 and 8 mg/kg/day, po, of indomethacin alone. Lethality was observed with doses of indomethacin from 5 to 8 mg/kg/day. Adverse gastrointestinal effects of aspirin, 32 to 500 mg/kg/day, po, were minimal (erythema and bleeding of the stomach mucosa and, on occasion, an intestinal ulceration); however, deaths occurred at 625 mg/kg and above. Polyarthritic rats were treated with various combinations of aspirin and indomethacin had significantly less gastrointestinal damage than animals treated with identical doses of indomethacin alone. Aspirin, 100 mg/kg and above, virtually abolished the dose-related indomethacin-induced gastrointestinal toxicity in the doses that were studied. At 32 mg/kg aspirin, the parallel shift in the indomethacin dose-toxicity curve suggested that the interaction between these two drugs is the result of competitive antagonism.     

Toxicity of lactide in dogs after 2 and 13 weeks of daily oral dosing.

Two-week and 13-week studies were conducted to determine the toxicity of lactide when the compound is administered orally in gelatin capsules to beagle dogs. In the 2-week study, daily doses of 0, 10, 100, 400, 1000 and 2500 mg/kg body weight/day were administered to dogs of both sexes for 14 consecutive days. All dogs survived to the end of the study. Clinical signs consistent with irritation of the alimentary tract occurred in dogs in the 1000 and 2500 mg/kg dose groups. Reductions in body weight gain and in absolute and relative thymus weights were observed in the same two dose groups, and reductions in absolute and relative spleen weights were seen in the 2500 mg/kg dose group. These changes were considered to be secondary to the stress resulting from irritation of the gastrointestinal tract. Gross and microscopic lesions were indicative of irritation, and included dark foci and haemorrhage of the stomach lining, and erosion and ulceration of the stomach and the oesophagus. Also noted in all high-dose dogs was renal tubular regeneration, which may represent repair of previous necrosis of the tubular epithelium. In the 13-week study, no deaths occurred when dogs were given daily oral doses of 0, 4, 20 or 100 mg/kg body weight/day. No clinical signs of toxicity were observed, and the compound had no effect on body weights, food consumption, or any of the clinical chemistry, haematology or urinalysis parameters assessed. Gross and microscopic findings considered to be potentially related to lactide administration were minimal, and included a stomach focus in one dog of each sex in the 100 mg/kg group. The stomach focus in the 100 mg/kg female dog was manifested microscopically as a stomach ulcer. Based on these results, the primary toxic effect of lactide was considered to be irritation of the gastrointestinal tract, and the no-observed-adverse-effect level (NOAEL) after subchronic oral dosing in dogs was considered to be 100 mg/kg/day.     

Toxic effects and excretion in urine of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in the rat after a single oral dose

Toxic effects and excretion in urine of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), the potent mutagenic compound in chlorinated drinking water, was evaluated in male Wistar rats by the up-and-down method. MX was dosed by gavage in deionized water at doses between 200 mg/kg and 600 mg/kg, for one animal at a time, and effects were observed for 14 days. Urine was collected in metabolism cages up to 72 h after dosing for chemical analysis of MX in urine. The animals receiving 200 mg/kg did not display clear clinical signs but at higher doses the signs of ill effects included dyspnea, laborious, wheezing and gasping breathing, decreased spontaneous motor activity, ataxia, nostril discharges, catalepsia and cyanosis. In necropsy bronchi contained foamy liquid and the lungs appeared edematous and spongy. The stomach cavity was expanded due to accumulation of fluid and gas and the gastrointestinal tract from stomach to caecum was reddish. Microscopically, the main target organ of toxicity was the gastrointestinal tract (diffuse congestion and necrosis in the mucosa). Signs of toxicity were recorded also in lungs (slight edema) and kidneys (dilated tubules, thin tubular epithelium, brownish tubular and interstitial concretion). The LD₅₀ in 48 h was 230 mg/kg. Only 0.03 – 0.07% of the dose (200 mg/kg or 300 mg/kg) was excreted in urine as intact MX. The results indicate that at high doses MX has a strong local irritating effect in the gastrointestinal tract and it probably increases liquid permeability in lungs. MX may also cause tubular damage in kidneys. Data also indicate that after an oral dose only traces of MX are excreted in urine as intact compound, suggesting that MX is subjected to intense metabolism before excretion, even at lethal doses. Received: 14 December 1993/Accepted: 28 February 1994     

Effects of a new 1,4-dihydropyridine, lacidipine, on gastrointestinal motility and other gastrointestinal functions

Lacidipine is a new 1,4-dihydropyridine calcium entry blocker endowed with slow onset of action and potent and long-lasting antihypertensive activity. This study investigated the effect of lacidipine on some gastrointestinal functions, mainly gastrointestinal motility, in rats and dogs. In fasting conscious dogs chronically fitted with electrodes and strain gauges along the small bowel, lacidipine (12 micrograms/kg i.v. bolus or 10 micrograms/kg/h for 3 h) did not modify the migrating motor complex pattern or intestinal spike activity. In the rat, lacidipine proved less active (ED 50 greater than 100 mg/kg p.o.) than nitrendipine (ED 50 = 31 mg/kg p.o.) in inhibiting gastric emptying of a liquid meal, whereas the opposite was true after a solid meal (ED 50 = 10.9 and 35.0 mg/kg p.o., respectively). Lacidipine inhibited fecal pellet output at lower doses (ED 50 = 14.8 mg/kg p.o.) than nitrendipine (ED 50 = 40.1 mg/kg p.o.). On histamine-induced gastric acid secretion, the effect of 100 micrograms/kg i.v. lacidipine was moderate (maximum inhibition 45%). The gastrointestinal effects displayed by lacidipine appear at doses at least 5 and 50 times as high as those affecting blood pressure after intravenous and oral administration, respectively. Thus, lacidipine is unlikely to cause noteworthy unwanted effects on the gastrointestinal tract.     

The effect of itazigrel and aspirin on the mucosa of the esophagus, stomach, and duodenum of normal subjects

The effects of aspirin, itazigrel (U-53,059; a new antiplatelet drug), and placebo on the mucosa of the esophagus, stomach, and duodenum were evaluated in this double-blind, randomized, placebo-controlled study. Six normal male subjects were included in each of five treatment groups: aspirin (325 mg each morning for five doses), aspirin (325 mg tid for 12 doses), itazigrel (25 mg each morning for five doses), itazigrel (50 mg tid for 12 doses), and placebo. Aspirin and itazigrel, at all doses investigated, significantly inhibited ex vivo, ionophore (A23187)-stimulated thromboxane B2 synthesis. Collagen-induced platelet aggregation was significantly inhibited on day 3 (P = .021) and day 5 (P = .002) in both aspirin and itazigrel groups as compared with placebo. Upper gastrointestinal endoscopy was performed before the first dose of drug (day 1) and two hours after the last dose (day 5) for each subject. A rating scale was used to score the amount of mucosal damage. The baseline (day 1) endoscopic scores revealed no significant differences between groups. On day 5, neither placebo nor itazigrel treatment groups showed any significant change compared with baseline. On day 5, both aspirin groups had significantly (P less than .001) more mucosal damage than the placebo group and either itazigrel group. It is concluded that in this relatively acute study, at doses that produce comparable inhibition of platelet aggregation and platelet cyclo-oxygenase, itazigrel was superior to aspirin in terms of toxicity to the upper gastrointestinal tract.     

Preclinical study of the safety of the antihistaminic preparation dimebon

The antihistaminic drug dimebon was subjected to toxicological study. It was demonstrated that as regards the level of the mean lethal doses dimebon can be attributed to little toxic substances. Administration of the drug in the doses approximating the therapeutic ones (1 and 5 mg/kg) for 2 months did not produce any alterations in rats, guinea-pigs or dogs. When administered in high doses (10 and 70 mg/kg) the drug provoked compensated abnormalities of some functions of the liver and kidneys in the presence of moderate and reversible structural changes in these organs. Dimebon did not exert any local irritating effect on the gastrointestinal tract. Administration of the drug in doses of 150 and 300 mg/kg at different times of pregnancy (days 1-7, 8-13, 14-19) did not produce any embryolethal or teratogenic effects.     

小鼠急性铊中毒半数致死剂量的测定

目的测定硝酸亚铊急性中毒小鼠的半数致死剂量（median lethal dose,LD50）。方法 130只小鼠随机分为13组,每组10只,雌雄各半,给小鼠经口灌入不同剂量的硝酸亚铊水溶液,观察并记录2周内各组小鼠症状、毒性反应及死亡情况,观察死亡小鼠肠道的组织病理学变化。以小鼠死亡率为指标,按改良寇氏法计算其LD50及95%置信区间,并统计不同性别中毒小鼠的死亡情况。结果 87 mg/kg染毒剂量组小鼠1周内全部死亡,硝酸亚铊急性中毒小鼠的LD50值为31.02 mg/kg,95%置信区间为29.47~32.57 mg/kg,主要对肠道产生严重损伤。不同性别铊中毒小鼠的死亡率无显著性差异。结论铊经胃肠道吸收后对肠道损害明显,对雌雄小鼠的毒性无明显差异。     

阿司匹林对胃肠黏膜损伤ICAM-1表达的临床研究

目的：探讨阿司匹林对胃肠黏膜损伤ICAM-1表达的临床意义。方法：应用免疫组化检测ICAM-1在大鼠胃黏膜细胞的表达。结果：实验组应用5.021mg/kg阿司匹林灌胃3d后,开始出现胃黏膜损伤的表现,损伤指数为（9.07±0.64）mm,14d损伤达高峰,损伤指数为（23.49±0.57）mm。免疫组化结果显示ICAM-1在用药后3d开始表达,7d后逐渐升高,21d达高峰,28d及35d仅有少量表达。实验组用药后与用药前比较ICAM-1表达水平有明显差异;对照组与实验组比较,ICAM-1均明显呈低水平表达。结论：在阿司匹林引起的胃黏膜损伤过程中ICAM-1的表达有一定的临床意义。阿司匹林对胃黏膜有较为明显的损伤,具有一定的危险性。     

Effects of aspirin, prednisolone and indomethacin on nephrotoxic serum nephritis in the rat.

1 The effects of aspirin, prednisolone, and indomethacin on nephrotoxic serum nephritis in rats was studied. The nephritis was induced by a single intravenous injection of nephrotoxic serum (NTS, rabbit anti-serum against the water-soluble renal antigen of the rat). The injection of NTS induced the heterologous phase of proteinuria (within a day after NTS injection) and then the autologous phase (5 to 7 days after NTS injection). The effect of drugs given before the NTS (i.e. prophylactically) or after the NTS (i.e. therapeutically) was investigated. 2 Aspirin, which was given orally at doses of 150 and 250 mg/kg daily from the day before NTS injection, suppressed the development of proteinuria in both the heterologous and the autologous phase, and lowered the serum cholesterol level towards the normal level. Aspirin (250 mg/kg daily, orally) had no significant effect against the established proteinuria in the autologous phase. 3 Prednisolone, which was given orally at doses of 3 and 5 mg/kg daily from the day before NTS injection, elevated the proteinuria in the heterologous phase, while inhibiting the development of proteinuria in the autologous phase. Prednisolone (5 mg/kg daily, orally) was ineffective against established proteinuria in the autologous phase. 5 Indomethacin (3 mg/kg daily, orally) did not exert any significant effect on proteinuria in either the heterologous or the autologous phase.     

Gastrointestinal microbleeding associated with the use of etodolac, ibuprofen, indomethacin, and naproxen in normal males

Etodolac, a nonsteroidal antiinflammatory and analgesic drug, was used in a randomized, parallel group, open-label design study, with stool analysis conducted in a blind fashion, to compare its effect in normal men in doses of 400 mg (N = 11) and 600 mg (N = 12) b.i.d. on gastrointestinal microbleeding with that of 600 mg ibuprofen, q.i.d. (N = 12), 50 mg indomethacin in the morning, 50 mg at noon, and 100 mg h.s. (N = 9), and 375 mg naproxen b.i.d. (N = 9). Etodolac was given at about 2 1/2 and 3 1/2 times the mean effective dose used for treating patients with rheumatoid arthritis. The other drugs were given at their manufacturers' maximum recommended doses. Lead-in placebo was given for one week, active drug for one week, and washout placebo for one week. Fecal blood loss was measured by the 51Cr-tagged red cell method, and was averaged over days 4-7 (baseline), 11-14 (treatment period), and 17-20 (washout). The mean increase in blood loss for the treatment period for the 400 mg etodolac b.i.d. group (0.13 ml) and 600 mg etodolac b.i.d. group (0.10 ml) was significantly less (P = 0.001) than the corresponding values for ibuprofen (1.14 ml), indomethacin (1.20 ml), and naproxen (0.87 ml). There was no tendency for greater blood loss at higher doses of etodolac. Etodolac at doses in excess of the mean effective dose in osteoarthritis and rheumatoid arthritis caused significantly less microbleeding in normal male volunteers during the seven-day treatment period than the other drugs tested, and not clinically more than that occurring during baseline placebo.