caa a22 4500 475819373 CHVBK 20180406123818.0 cr unu---uuuuu 170329e20001201xx s 000 0 eng 10.1007/s002280000206 doi (NATIONALLICENCE)springer-10.1007/s002280000206 Pharmacokinetics of esomeprazole after oral and intravenous administration of single and repeated doses to healthy subjects [Elektronische Daten] [M. Hassan-Alin, T. Andersonn, E. Bredberg, K. Röhss] Abstract.: Objective: To study the pharmacokinetics of esomeprazole, one of the optical isomers of omeprazole, after 20mg or 40mg single and repeated oral and intravenous administration to healthy subjects. The main metabolites of esomeprazole were also assessed after the 40-mg oral dose. Methods: In two separate studies, 16 healthy male subjects and 16 healthy male and female subjects received intravenous doses of 20mg and 40mg esomeprazole, respectively, on the first investigation day. After a wash-out period of 5-14days, the same doses (20mg as a solution and 40mg as a capsule) were given orally for 5days and then again intravenously on day6. Blood samples for determination of esomeprazole and its metabolites were collected 12h or 24h post-dose and were analysed using normal-phase liquid chromatography with ultraviolet (UV) detection. Pharmacokinetic parameters of esomeprazole and its metabolites were estimated using non-compartmental analysis. Geometric means and ratios of the geometric means together with 95% confidence intervals (CI) of the pharmacokinetic parameters were calculated using analysis of variance (ANOVA). Results: Plasma clearance (CL) of esomeprazole decreased from 22l/h to 16l/h and from 17l/h to 9l/h following repeated dosing of 20mg and 40mg, respectively. Total area under the plasma concentration-time curve (AUC) increased (from 1.34µmol×h/l to 2.55µmol×h/l) with absolute bioavailability (F) being 50% on day1 and 68% on day5 after the 20-mg oral dose. AUC increased (from 4.32µmol×h/l to 11.21µmol×h/l) with F being 64% on day1 and 89% on day5 after the 40-mg oral dose. The plasma levels for esomeprazole sulphone were substantially higher on day5 than on day1, while those for 5-hydroxy esomeprazole were marginally higher on day5 than on day1 following repeated oral dosing of 40mg esomeprazole. No side effects attributable to esomeprazole were noticed. Conclusion: The increased AUC of esomeprazole with repeated dosing is probably due to a combination of a decreased first-pass elimination and a decreased systemic clearance. Springer-Verlag, 2000 Esomeprazole Pharmacokinetics Single dose Steady state nationallicence Hassan-Alin M. Experimental Medicine, AstraZeneca Research and Development Mölndal, S-431 83 Mölndal, Sweden aut Andersonn T. Clinical Pharmacology, AstraZeneca LP, Wayne, PA, USA aut Bredberg E. Gastrointestinal Therapeutic Area, AstraZeneca Research and Development Mölndal, S-431 83 Mölndal, Sweden aut Röhss K. Gastrointestinal Therapeutic Area, AstraZeneca Research and Development Mölndal, S-431 83 Mölndal, Sweden aut European Journal of Clinical Pharmacology Springer-Verlag 56/9-10(2000-12-01), 665-670 0031-6970 56:9-10<665 2000 56 228 https://doi.org/10.1007/s002280000206 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280000206 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hassan-Alin M. Experimental Medicine, AstraZeneca Research and Development Mölndal, S-431 83 Mölndal, Sweden aut NATIONALLICENCE 700 1- Andersonn T. Clinical Pharmacology, AstraZeneca LP, Wayne, PA, USA aut NATIONALLICENCE 700 1- Bredberg E. Gastrointestinal Therapeutic Area, AstraZeneca Research and Development Mölndal, S-431 83 Mölndal, Sweden aut NATIONALLICENCE 700 1- Röhss K. Gastrointestinal Therapeutic Area, AstraZeneca Research and Development Mölndal, S-431 83 Mölndal, Sweden aut NATIONALLICENCE 773 0- European Journal of Clinical Pharmacology Springer-Verlag 56/9-10(2000-12-01), 665-670 0031-6970 56:9-10<665 2000 56 228 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer