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

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.