CIRCADIAN ASPECTS OF DICLOFENAC GASTRODUODENOPATHY AND ROXATIDINE PROPHYLAXIS

The gastrointestinal side-effect profile of non-steroidal anti-inflammatory drugs should follow a circadian rhythm. In a randomized, parallel, double-blind study the gastric duodenal effects of 100 mg diclofenac retard daily in the presence and absence of 150 mg roxatidine was evaluated in 20 healthy volunteers undergoing upper GI-endoscopy. Drugs were taken over a period of 14 days either at 8 a.m. (n = 10) or at 8 p.m. (n = 10). Endoscopic controls were performed at entry and repeated after 14 days of treatment. A damaging score according to Lanza et al. was used. At entry both groups showed comparable mucosal damages: 8 a.m.-group: placebo 0.9+/-0.1 (+SEM), roxatidine 0.9+/-0.1; 8 p.m.-group: placebo 1.0+/-0.0, roxatidine 0.9+/-0.1. After 14 days of treatment the lesion score increased in the diclofenac retard/placebo-group in the 8 a.m.-group to 7.6+/-1.9 and in the 8 p.m.-group to 7.2+/-1.1. The corresponding values in the diclofenac/roxatidine-group were 2.1+/-0.9 (8 a.m.-group) and 1.4+/-0.4 (8 p.m.-group). This protection afforded by roxatidine was significant when compared with placebo (p < 0.05). Our data suggest that the gastrolesive effects of diclofenac retard are independent of the time of drug ingestion; in addition, protection by roxatidine was also time-independent.