P. Muller et al., CIRCADIAN ASPECTS OF DICLOFENAC GASTRODUO DENOPATHY AND ROXATIDINE PROPHYLAXIS, Zeitschrift fur Rheumatologie, 52(5), 1993, pp. 297-300
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.