Su1615 Effect of Intravenous Proton-Pump Inhibitor (Omeprazole) on Intra-Gastric pH in Thai Healthy Volunteers With Extensive Metabolizing CYP2C19 Genotype: Comparison Between Intermittent Bolus (Low Dose) and Continuous Infusion (Standard Recommended Dose)

Abstract

BACKGROUNDS AND AIMS: Proton-pump inhibitor is more effective for gastric acid control in Asian than Western population possible because of high prevalence of poor metabolizing CYP2C19 genotype in Asian people. The aim of this study was to evaluate the effect of low dose intravenous (IV) bolus vs. standard recommended dose continuous IV infusion of omeprazole in Thai healthy volunteers with extensive metabolizing CYP2C19 genotype. METHODS: 8 healthy subjects (age 30±6yr, 5 F, BMI 24±3 kg/m2) with extensive metabolizing CYP2C19 genotype were randomized to receive either omeprazole 80mg IV bolus followed by 40 mg IV bolus every 12 hr or omeprazole 80mg IV bolus followed by 8mg/ hr continuous infusion for 48 hr. The gastric pH was monitored by a pH catheter with a data logger (DIGITRAPPER pH 400, Medtronic A/S) for 2 days during the omeprazole treatment peroids. The gastric pH sensor was positioned at 10 cm below the lower esophageal sphincter located by esophageal manometry. All subjects were allowed to consume 3 standard meals/day. RESULTS : The mean gastric pH for IV bolus was significantly lower than continuous infusion only on day 1 [6.2±1.0 vs. 7.1±0.6 (p 6 for IV bolus was also significantly lower compared to continuous infusion only on day 1(66.2±22.7% vs. 84.7±17.3%)(p 6 for the entire 48-hr study was significantly lower for IV bolus compared to continuous infusion (69.9±12.6% vs. 83.0±13.8%, p 24 had similar intragastric pH during both IV bolus and IV continuous infusion of omeprazole (IV bolus, BMI 24: 6.4±0.9 vs. 6.3±0.4) (continuous drip; 7.1±0.3 vs. 6.8±0.6)(p>0.05). CONCLUSION: Continuous IV infusion of standard recommended dose of omeprazole provided better gastric acid control compared to lower dose IV bolus only during the first day but not on the second day. Although the continuous IV infusion was more effective both standard dose continuous IV infusion and low dose IV bolus omeprazole was effective for gastric pH control in Thai healthy volunteers with extensive metabolizing CYP2C19 genotypes. The better gastric acid control compared to those reported in healthy volunteers in Western countries suggests the role of other factor(s), beside the CYP2C19 genotype, on gastric acid inhibition effect of IV omeprazole.