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Clinical Drug Investigation
Published in: Clinical Drug Investigation 10/2011

01-10-2011 | Original Research Article

Effect of Fluoxetine on the Pharmacokinetics of Lansoprazole

A Two-Treatment Period Study in Healthy Male Subjects

Authors: Dr Laurian Vlase, PhD, Adina Popa, Maria Neag, Dana Muntean, Sorin E. Leucuta

Published in: Clinical Drug Investigation | Issue 10/2011

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Abstract

Background: Fluoxetine is an inhibitor of the main metabolizing enzymes of lansoprazole and could influence the pharmacokinetics of lansoprazole. The changes in lansoprazole pharmacokinetics could have clinical significance concerning the safety of the therapy.
Objective: The aim of this study was to evaluate the pharmacokinetic interaction between fluoxetine and lansoprazole in healthy subjects.
Methods: A dose of lansoprazole 30mg, alone or in combination with fluoxetine 60mg, was administered to 18 healthy male subjects in a two-treatment study design, separated by an 8-day period in which fluoxetine alone was administered as a single oral daily dose. Plasma concentrations of lansoprazole were determined during a 12-hour period following drug administration. Lansoprazole plasma concentrations were determined by a validated liquid chromatography-mass spectrometry method. The pharmacokinetic parameters of lansoprazole were calculated using non-compartmental analysis.
Results: In the two periods of treatment, the mean maximum plasma concentration (Cmax) values were 817ng/mL (lansoprazole alone) and 1370 ng/mL (lansoprazole in combination with fluoxetine after pre-treatment with fluoxetine for 8 days) [p<0.0001]. The observed area under the plasma concentration-time curve (AUC) from time zero to time of last measurable concentration values were 2400 and 6220 ng · h/mL (p < 0.0001), respectively, and the AUC from time zero to infinity values were 2480 and 7290 ng · h/mL (p<0.0001), respectively. The time to reach Cmax values were 2.72 and 2.64 hours, respectively. The elimination rate constant from the central compartment values were 0.50 and 0.21 h-1, respectively (p<0.0001). The elimination half-life values were 1.47 and 3.56 hours (p < 0.0001), respectively, and the mean residence times were 4.0 and 6.9 hours (p < 0.0001), respectively.
Conclusion: The data demonstrate a pharmacokinetic interaction between fluoxetine and lansoprazole and suggest that the observed interaction may be clinically significant, although its clinical relevance has yet to be confirmed.
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Metadata
Title
Effect of Fluoxetine on the Pharmacokinetics of Lansoprazole
A Two-Treatment Period Study in Healthy Male Subjects
Authors
Dr Laurian Vlase, PhD
Adina Popa
Maria Neag
Dana Muntean
Sorin E. Leucuta
Publication date
01-10-2011
Publisher
Springer International Publishing
Published in
Clinical Drug Investigation / Issue 10/2011
Print ISSN: 1173-2563
Electronic ISSN: 1179-1918
DOI
https://doi.org/10.2165/11589010-000000000-00000

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