title: Pharmacokinetics of esomeprazole following varying intravenous administration rates.
abstract: There are situations where the use of an oral proton pump inhibitors is not possible. In such situations an intravenous route is the preferred alternative. An intravenous formulation of esomeprazole has recently been developed. This study was designed to evaluate the pharmacokinetics and tolerability of single-dose intravenous esomeprazole using different rates of administration. The study was an open randomised, cross-over design in healthy male and female (n = 24). Esomeprazole 40 mg intravenously was administrated as an infusion over 10, 15, 20 or 30 min., or esomeprazole 20 mg intravenously as an injection over 3 min. There was a wash-out period of at least 6 days between dose regimens. It was demonstrated that increasing the rate of intravenous infusion of esomeprazole 40 mg resulted in higher Cmax values (geometric means; 5.2-7.6 micromol/l), but the AUC values remained relatively constant (7.1-7.2 micromor/l). As expected esomeprazole 20 mg administered as a 3 min. intravenous injection had lower Cmax (3.6 micromol/l) and AUC (2.9 micromol.r/l) values than any of the infusions of esomeprazole 40 mg. Intravenous esomeprazole was well tolerated in this study. In conclusion, any variation in the infusion rate of esomeprazole 40 mg intravenously has little effect on the pharmacokinetics of esomeprazole in healthy volunteers, which provides flexibility in the choice of dosing regimens.
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden. mohammad.niazi@astrazeneca.com
authors.forename: Mohammad
authors.initials: M
authors.lastname: Niazi
authors.forename: Henrik
authors.initials: H
authors.lastname: Ahlbom
authors.forename: Patrik
authors.initials: P
authors.lastname: Bondarov
authors.forename: Anna H
authors.initials: AH
authors.lastname: Karlsson
authors.forename: Mohammed
authors.initials: M
authors.lastname: Hassan-Alin
authors.forename: Hans
authors.initials: H
authors.lastname: Rydholm
authors.forename: Kerstin
authors.initials: K
authors.lastname: Röhss
mesh_terms: D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D064098:Esomeprazole / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D054328:Proton Pump Inhibitors
chemical_list: D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D064098:Esomeprazole