EFFECTS OF RANITIDINE AND CISAPRIDE ON ACID REFLUX AND ESOPHAGEAL MOTILITY IN PATIENTS WITH REFLUX ESOPHAGITIS - A 24-HOUR AMBULATORY COMBINED PH AND MANOMETRY STUDY

The effect of ranitidine and cisapride on acid reflux and oesophageal motility was investigated in 18 patients with endoscopically verified erosive reflux oesophagitis. Each patient was treated with placebo, ra nitidine (150 mg twice daily), and ranitidine (150 mg twice daily) plu s cisapride (20 mg twice daily) in a double blind, double dummy, withi n subject, three way cross over design. Oesophageal acidity and motili ty were monitored under ambulatory conditions for 24 hours on the four th day of treatment, after a wash out period of 10 days during which p atients received only antacids for relief of symptoms. Acid reflux was monitored by a pH electrode located 5 cm above the lower oesophageal sphincter. Intra-oesophageal pressure was simultaneously recorded from four transducers placed 20, 15, 10, and 5 em above the lower oesophag eal sphincter. Upright reflux was three times higher than supine reflu x (median (range) 13.3 (3.7-35.0)% v 3.7 (0.37-6)% of the time with pH <4.0, p<0.01, n=18). Compared with placebo, ranitidine decreased total reflux (from 10.0 (3.2-32.6)% to 6-4 (1-2-22.9)%, p<0.01), upright re flux (p<0.05), supine reflux (p<0.001), and postprandial reflux (p<0.0 1), but did not affect oesophageal motility. The combination of raniti dine with cisapride further diminished the acid reflux found with rani tidine - that is, cisapride led to an additional reduction of total re flux (from 6-4 (1.2-22-9)% to 3.7 (1-0-12.7)%, p<0.01), supine reflux (p<0.05), and postprandial reflux (p<0.05). Cisapride also reduced bot h the number (p<0.01) and duration (p<0.05) of reflux episodes and sig nificantly increased amplitude, duration, and propagation velocity of oesophageal contractions (p<0.05) but did not affect the number of con tractions. The findings show that the 30% reduction of oesophageal aci d exposure achieved by a conventional dose of ranitidine (150 mg twice daily) can be improved to more than 60% by combination with cisapride (20 mg twice daily). The cisapride induced increase in oesophageal co ntractile force and propagation velocity seems to enhance the clearanc e of gastro-oesophageal reflux. Combination of a histamine H-2 recepto r antagonist with a prokinetic agent may therefore provide an alternat ive treatment for reflux oesophagitis.