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Identification of a Single Time-point for Plasma Lansoprazole Measurement That Adequately Reflects Area Under the Concentration-Time Curve

Niioka, Takenori MD, PhD*; Yasui-Furukori, Norio† ‡; Uno, Tsukasa* †; Sugawara, Kazunobu*; Kaneko, Sunao; Tateishi, Tomonori

Therapeutic Drug Monitoring: June 2006 - Volume 28 - Issue 3 - p 321-325
doi: 10.1097/01.ftd.0000211835.18973.e3
Short Communication
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The objective of this study was to identify a single time-point for plasma lansoprazole measurement that adequately reflects area under the plasma lansoprazole concentration-time curve (AUC) after administration of lansoprazole alone or together with coadministration with CYP mediators. A randomized double-blind placebo-controlled crossover study design in 3 phases was conducted at intervals of 2 weeks. Eighteen healthy Japanese volunteers, comprising 3 CYP2C19 genotype groups, took a single oral 60-mg dose of lansoprazole after three 6-day pretreatments, that is, clarithromycin 800 mg/d, fluvoxamine 50 mg/d, and placebo. Blood samplings (10 mL each) for determination of lansoprazole were taken up to 24 hours after the administration of lansoprazole. Correlation between plasma lansoprazole concentrations at various time points and AUC0–24 were analyzed. Although there were significant differences in the pharmacokinetic parameters of lansoprazole during clarithromycin and placebo among CYP2C19 genotypes, the differences were not found during fluvoxamine. The plasma concentrations 3, 4, 6, and 8 hours after administration (C3, C4, C6, and C8, respectively) were highly correlated with AUC0–24 in coadministration with placebo, clarithromycin, and fluvoxamine (r>0.8, P<0.001). In particular, C6 showed a correlation coefficient of 0.940, 0.992, and 0.953 in coadministration with placebo, clarithromycin, and fluvoxamine, respectively, and was the most appropriate for estimating AUC0−24. The present study demonstrates that AUC of lansoprazole can be estimated by using a single time-point at C6. This method of plasma concentration monitoring at one time-point might be more suitable for AUC estimation than reference to CYP2C19 genotypes, particularly in coadministration of CYP mediators.

*Department of Pharmacy, Hirosaki University Hospital

Department of Clinical Pharmacology, Hirosaki University School of Medicine

Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan

Supported in part by a grant from Aid for Scientific Research (No. 17923049).

Reprints: Norio Yasui-Furukori, MD, PhD, Department of Neuropsychiatry, Hirosaki University, School of Medicine, Hirosaki 036-8562, Japan (e-mail: yasufuru@cc.hirosaki-u.ac.jp)

Received for publication July 18, 2005; accepted November 22, 2005

© 2006 Lippincott Williams & Wilkins, Inc.