BACKGROUND:Esomeprazole provides effective and long lasting inhibition of gastric acid secretion. However, the pharmacokinetics and pharmacodynamics of intravenous esomeprazole in the Chinese population remain unclear. AIM: To compare the pharmacokinetics and pharmacodynamics of intravenous esomeprazole (injection and infusion) and their clinical safety and tolerability in healthy Chinese subjects. METHODS: A randomized, single-center, open-label, five-way crossover study was conducted in 20 healthy volunteers. CYP2C19 metabolizer genotype and Helicobacter pylori status were examined. Five dosing regimens were used: single 40 mg injection, 40 mg infusion every 12 h, 40 mg infusion followed by continuous infusion at 8 mg/h, 80 mg infusion followed by continuous infusion at 4 or 8 mg/h. Intragastric pH was recorded within 24 h. Plasma concentration-time curve, maximum plasma concentration (Cmax ), steady state concentration, and total plasma clearance were determined. Adverse events were also recorded. RESULTS: Continuous infusion resulted in a higher mean area under the curve and Cmax than injection. There were no significant differences among the four infusion groups in terms of percentages of time at pH > 4, > 5, > 6, > 7 within 24 h and pH > 6 within the first 3 h. There were no significant differences in pharmacokinetic or pH values among variants of CYP2C19 genotype. The pH value within 24 h was unaffected by H. pylori infection in subjects with continuous infusion. CONCLUSIONS:Esomeprazole administrated by infusion produces better pharmacokinetic and intragastric pH profiles compared with those by injection. The optimal administration schedule for esomeprazole in Chinese subjects is infusion with 40 mg/12 h.
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BACKGROUND:Esomeprazole provides effective and long lasting inhibition of gastric acid secretion. However, the pharmacokinetics and pharmacodynamics of intravenous esomeprazole in the Chinese population remain unclear. AIM: To compare the pharmacokinetics and pharmacodynamics of intravenous esomeprazole (injection and infusion) and their clinical safety and tolerability in healthy Chinese subjects. METHODS: A randomized, single-center, open-label, five-way crossover study was conducted in 20 healthy volunteers. CYP2C19 metabolizer genotype and Helicobacter pylori status were examined. Five dosing regimens were used: single 40 mg injection, 40 mg infusion every 12 h, 40 mg infusion followed by continuous infusion at 8 mg/h, 80 mg infusion followed by continuous infusion at 4 or 8 mg/h. Intragastric pH was recorded within 24 h. Plasma concentration-time curve, maximum plasma concentration (Cmax ), steady state concentration, and total plasma clearance were determined. Adverse events were also recorded. RESULTS: Continuous infusion resulted in a higher mean area under the curve and Cmax than injection. There were no significant differences among the four infusion groups in terms of percentages of time at pH > 4, > 5, > 6, > 7 within 24 h and pH > 6 within the first 3 h. There were no significant differences in pharmacokinetic or pH values among variants of CYP2C19 genotype. The pH value within 24 h was unaffected by H. pylori infection in subjects with continuous infusion. CONCLUSIONS:Esomeprazole administrated by infusion produces better pharmacokinetic and intragastric pH profiles compared with those by injection. The optimal administration schedule for esomeprazole in Chinese subjects is infusion with 40 mg/12 h.