CIRCADIAN ASPECTS OF DICLOFENAC GASTRODUO DENOPATHY AND ROXATIDINE PROPHYLAXIS

The gastrointestinal side-effect profile of non-steroidal anti-inflamm atory drugs should follow a circadian rhythm. In a randomized, paralle l, double-blind study the gastric duodenal effects of 100 mg diclofena c retard daily in the presence and absence of 150 mg roxatidine was ev aluated 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 repeate d after 14 days of treatment. A damaging score according to Lanza et a l. 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.-gr oup: placebo 1.0+/-0.0, roxatidine 0.9+/-0.1. After 14 days of treatme nt the lesion score increased in the diclofenac retard/placebo-group i n 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 affo rded by roxatidine was significant when compared with placebo (p < 0.0 5). Our data suggest that the gastrolesive effects of diclofenac retar d are independent of the time of drug ingestion; in addition, protecti on by roxatidine was also time-independent.