Simon B, Koch E M, Jackisch P, Müller P
Kreiskrankenhaus Schwetzingen.
Arzneimittelforschung. 1993 Sep;43(9):989-91.
Circadian Dependency of Ibuprofen Gastropathy and Protective Effect of Ranitidine/An endoscopic, controlled double-blind pilot study. In a randomized parallel double-blind study, the gastric and duodenal effects of 600 mg S(+)-ibuprofen (CAS 15687-27-1) daily in the presence and absence of 300 mg ranitidine (CAS 66357-35-5) was evaluated in 20 healthy volunteers undergoing upper GI-endoscopy. Drugs were taken over a period of 7 days either at 8 a.m. (n = 10) or at 8 p.m. (n = 10). Endoscopic controls were performed at entry and repeated after 7 days of treatment. A damage score according to Lanza et al. was used. At entry both groups showed comparable mucosal damages. 8 a.m.-group: ibuprofen/placebo (stomach) 0.9 +/- 0.1 and 0.0 +/- 0.0 (duodenum); ibuprofen/ranitidine 0.8 +/- 0.1 (stomach) and 0.1 +/- 0.1 (duodenum). 8 p.m.-group: ibuprofen/placebo 0.9 +/- 0.1 (stomach) and 0.2 +/- 0.1 (duodenum); ibuprofen/ranitidine 0.9 +/- 0.1 (stomach) and 0.1 +/- 0.1 (duodenum). After 7 days of treatment the lesion score increased in the ibuprofen/placebo-group in the 8 a.m.-group to 3.2 +/- 1.2 (stomach) and to 0.7 +/- 0.5 (duodenum), and in the 8 p.m.-group to 8.4 +/- 1.9 (stomach) and to 2.9 +/- 1.2 (duodenum). The corresponding values in the ibuprofen/ranitidine-group were 1.8 +/- 0.8 (stomach) and 0.1 +/- 0.1 (duodenum) (8 a.m.-group) as well as 5.1 +/- 1.4 (stomach) and 0.1 +/- 0.1 (duodenum) (8 p.m.-group). The difference between the morning and the evening dose of ibuprofen as well as ranitidine protection reached statistical significance when the corresponding data were pooled (p < 0.05). Our data suggest that the gastrolesive effects of S(+)-ibuprofen are dependent of the time of drug ingestion; protection by ranitidine, however, was time-independent.
一项内镜对照双盲试验研究。在一项随机平行双盲研究中，对20名接受上消化道内镜检查的健康志愿者，评估了每日600mg S(+)-布洛芬（CAS 15687-27-1）在有或无300mg雷尼替丁（CAS 66357-35-5）情况下对胃和十二指肠的影响。药物服用7天，一组在上午8点（n = 10）服用，另一组在晚上8点（n = 10）服用。在入组时及治疗7天后进行内镜检查。采用兰扎等人的损伤评分标准。入组时两组黏膜损伤程度相当。上午8点组：布洛芬/安慰剂（胃）0.9±0.1，（十二指肠）0.0±0.0；布洛芬/雷尼替丁（胃）0.8±0.1，（十二指肠）0.1±0.1。晚上8点组：布洛芬/安慰剂（胃）0.9±0.1，（十二指肠）0.2±0.1；布洛芬/雷尼替丁（胃）0.9±0.1，（十二指肠）0.1±0.1。治疗7天后，上午8点组布洛芬/安慰剂组的病变评分在胃中升至3.2±1.2，在十二指肠中升至0.7±0.5；晚上8点组在胃中升至8.4±1.9，在十二指肠中升至2.9±1.2。布洛芬/雷尼替丁组相应值在上午8点组为（胃）1.8±0.8，（十二指肠）0.1±0.1；在晚上8点组为（胃）5.1±1.4，（十二指肠）0.1±0.1。将相应数据合并后，布洛芬早晚剂量的差异以及雷尼替丁的保护作用具有统计学意义（p < 0.05）。我们的数据表明，S(+)-布洛芬的致胃损伤作用取决于药物摄入时间；然而，雷尼替丁的保护作用与时间无关。
