A pharmacokinetic study comparing single and repeated oral doses of 20 mg and 40 mg omeprazole and its two optical isomers, 5-omeprazole (esomeprazole) and R-omeprazole, in healthy subjects
A pharmacokinetic study comparing single and repeated oral doses of 20 mg and 40 mg omeprazole and its two optical isomers, 5-omeprazole (esomeprazole) and R-omeprazole, in healthy subjects
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DOI：
10.1007/s00228-004-0841-1
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发表时间：
2005-01-01
影响因子：
2.9
通讯作者：
Röhss, K
中科院分区：
文献类型：
--
作者：
Hassan-Alin, M;Andersson, T;Röhss, K
目的：研究s -奥美拉唑（埃索美拉唑）、r -奥美拉唑和外消旋奥美拉唑分别单次和重复口服20 mg和40 mg在健康男性和女性体内的药代动力学。方法：在一项开放、随机、三方向交叉研究中，12名受试者接受20 mg口服溶液，另外12名受试者接受40 mg s-奥美拉唑、r -奥美拉唑和外消旋奥美拉唑口服溶液，每天1次，连续5天，间隔至少10天的洗脱期。在研究第1天和第5天给药后的12小时内，在给药前和选定的时间点采集血液样本进行分析。s -奥美拉唑、r -奥美拉唑的药动学参数。外消旋奥美拉唑和两种主要代谢物（5-羟基和磺胺酮）采用非区室分析计算。结果：给药20 mg后，s -奥美拉唑、r -奥美拉唑和外消旋奥美拉唑第1天的血浆浓度-时间曲线下总面积（AUC）分别为1.52、0.62和1.04 μ mol h/l。第5 d的AUC值分别为2.84、0.68和1.63 mu mol h/l。40 mg剂量后第1天对应值分别为3.88、1.39、2.44 μ mol h/l，第5天对应值分别为9.32、1.80、5.79 μ mol h/l。结论：s -奥美拉唑（埃索美拉唑，20 mg和40 mg）单次和重复给药后的AUC值均高于r -奥美拉唑或外消旋奥美拉唑，这是由于s -奥美拉唑的代谢率低于r -奥美拉唑，因此外消旋奥美拉唑。s -奥美拉唑、r -奥美拉唑和外消旋体耐受性良好。
Objective: To investigate the pharmacokinetics of S-omeprazole (esomeprazole), R-omeprazole and racemic omeprazole following single and repeated oral doses of 20 mg and 40 mg of each compound in healthy male and female subjects.Methods: In an open, randomised, three-way, cross-over study, 12 subjects received 20 mg and another 12 subjects received 40 mg S-omeprazole, R-omeprazolc and racemic omeprazole as oral solutions once daily for 5 days, separated by washout periods of at least 10 days. Blood samples were taken for analysis pre-dose and at selected time points during a 12-h period following drug administration on study day 1 and day 5. Pharmacokinetic parameters of S-omeprazole, R-omeprazole. racemic omeprazole and the two main metabolites (5-hydroxy and sulphone) were calculated using noncompartmental analysis.Results: Following the 20-mg dose of each compound, values of the total area under the plasma concentration-time curve (AUC) were 1.52, 0.62 and 1.04 mu mol h/l for S-omeprazole, R-omeprazole and racemic omeprazole, respectively, on day 1. Respectively, AUC values on day 5 were 2.84, 0.68 and 1.63 mu mol h/l. Corresponding values after the 40-mg doses were 3.88, 1.39 and 2.44 ltrnol h/l on day 1 and 9.32, 1.80 and 5.79 mu mol h/l on day 5.Conclusion: Treatment with S-omeprazole (esomeprazole; 20 mg and 40 mg) resulted in higher AUC values than with either R-omeprazole or racemic omeprazole after both single and repeated doses due to a lower metabolic rate of S-omeprazole than R-omeprazole and, consequently, racemic omeprazole. S-Omeprazole, R-omeprazole and the racemate were well tolerated.