The Effects of Increasing Doses of Ranitidine on Gastric pH in Children.

BACKGROUND: Ranitidine is widely used for gastroesophageal reflux disease (GERD) in children, but optimal dosing is unclear. We compared effects of weight-based doses of oral ranitidine on gastric pH in children with clinical GERD.

METHODS: Children ages 4-11 years with clinical GERD were enrolled in a multi-center prospective randomized study comparing a fixed dose of ranitidine (Zantac 75) with placebo after an overnight fast; gastric pH was measured for 6 h after the fixed dose (Phase 1). Of the six enrollees from our center, four received active drug during Phase 1; 12 h after the fixed dose, these four children received ranitidine 5 mg/kg (maximum 150 mg) and gastric pH was measured for another 6-12 hours (Phase 2). This report details the effects of two dose ranges (Low Dose, < 3 mg/kg/dose, and High Dose, ≥ 3 mg/kg/dose) on gastric pH in children.

RESULTS: The four children were 6.9-11.3 years old and weighed 20.4-49.5 kg. The Low Doses were 1.5-2.7 mg/kg; the High Doses were 3-5 mg/kg. Although the mean percentage of time with gastric pH > 4 during the entire 6 hours following dosing was similar after Low and High Dose (50% vs. 57%, NS), during the last two hours of this interval the mean percentage of time with gastric pH > 4 was only 29% for Low Dose vs. 89% for High Dose (P = 0.006). Moreover, during those two hours, none of the Low Doses kept gastric pH above 4 for > 60% of the time, while all of the High Doses kept pH above 4 for > 60% of the time (P = 0.03). In three of four patients who underwent extended (9-12 h) gastric pH monitoring after High Dose ranitidine, gastric pH was above 4 for more than 40% of total time.

CONCLUSIONS: Doses of ranitidine ≥ 3 mg/kg/dose may be required for acid suppression lasting beyond 6 hours.