Combined effect of pirenzepine and ranitidine on the nocturnal intragastric pH in non-responders to ranitidine.

Both H2-receptor antagonists and pirenzepine are used in the treatment of peptic ulcer disease. Since we have recently found a higher frequency of non-responders to H2-receptor antagonists among cirrhotics, we tested the effect of the combination of 50 mg pirenzepine and 300 mg ranitidine in 25 patients (12 cirrhotics and 13 controls) in whom a normal 300 mg dose of ranitidine had failed to suppress intragastric acidity. Nocturnal intragastric pH was continuously monitored for 12 hours. A rise in the intragastric pH above 4.0 for more than 6 hours following the oral dose at 18.00 h was considered as response. In all subjects, plasma concentrations of ranitidine and pirenzepine were in the therapeutic range. Coadministration of pirenzepine and ranitidine resulted in sufficient increase of the intragastric pH in only 4 of the 12 patients with cirrhosis, and in 4 of the 13 control patients. This treatment failure in most of our patients does not support the view that excessive vagal drive might play an important role in the non-response to H2-blockers. With regard to the benefit resulting from coadministration of pirenzepine and ranitidine, there seems to be no difference between cirrhotic and control patients.