CIRCADIAN DEPENDENCY OF IBUPROFEN GASTROP ATHY AND PROTECTIVE EFFECT OF RANITIDINE - AN ENDOSCOPIC, CONTROLLED DOUBLE-BLIND PILOT-STUDY

In a randomized parallel double-blind study the gastric and duodenal e ffects 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 ov er 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 en try both groups showed comparable mucosal damages. 8 a.m. group: ibupr ofen/placebo (stomach) 0.9 +/- 0.1 and 0.0 +/- 0.0 (duodenum); ibuprof en/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 (duode num); ibuprofen/ranitidine 0.9 +/- 0.1 (stomach) and 0.1 +/- 0.1 (duod enum). After 7 days of treatment the lesion score increased in the ibu profen/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 (sto mach) and to 2.9 +/- 1.2 (duodenum). The corresponding values in the i buprofen/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(+)-ibuprofe n are dependent of the time of drug ingestion; protection by ranitidin e, however, was time-independent.