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Pharmacokinetics, pharmacodynamics, and safety of esomeprazole injection/infusion in healthy C hinese volunteers: A five‐way crossover study
Author(s) -
Yang Hong,
Li Jingnan,
Zhao Qian,
Li Ji,
Shen Kai,
Yang Xiaoou,
Jiang Ji,
Hu Pei,
Qian Jiaming
Publication year - 2013
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12305
Subject(s) - pharmacokinetics , medicine , pharmacodynamics , esomeprazole , tolerability , crossover study , dosing , pharmacology , adverse effect , bioequivalence , population , gastroenterology , anesthesia , placebo , alternative medicine , pathology , environmental health
Background Esomeprazole provides effective and long lasting inhibition of gastric acid secretion. However, the pharmacokinetics and pharmacodynamics of intravenous esomeprazole in the C hinese population remain unclear. Aim To compare the pharmacokinetics and pharmacodynamics of intravenous esomeprazole (injection and infusion) and their clinical safety and tolerability in healthy C hinese subjects. Methods A randomized, single‐center, open‐label, five‐way crossover study was conducted in 20 healthy volunteers. CYP 2 C 19 metabolizer genotype and H elicobacter 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 ( C max ), 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 C max 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 CYP 2 C 19 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 C hinese subjects is infusion with 40 mg/12 h.