Population Pharmacokinetics and Proton Pump Inhibitory Effects of Intravenous Lansoprazole in Healthy Japanese Males
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- Sakurai Yuichi
- Graduate School of Pharmaceutical Sciences, University of Toyama Takeda Pharmaceutical Company Limited
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- Hirayama Masashi
- Takeda Pharmaceutical Company Limited
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- Hashimoto Muneaki
- Takeda Pharmaceutical Company Limited
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- Tanaka Takanori
- Ohsaki Clinic
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- Hasegawa Setsuo
- Sekino Clinical Pharmacology Clinic
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- Irie Shin
- Kyushu Clinical Pharmacology Research Clinic
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- Kayano Yuichiro
- Graduate School of Pharmaceutical Sciences, University of Toyama
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- Taguchi Masato
- Graduate School of Pharmaceutical Sciences, University of Toyama
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- Hashimoto Yukiya
- Graduate School of Pharmaceutical Sciences, University of Toyama
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Abstract
A total of 56 healthy Japanese males were enrolled in single- or multiple- dose pharmacokinetic trials of intravenous lansoprazole administration. The population pharmacokinetics of the drug was evaluated using nonlinear mixed effects model (NONMEM) software. In addition, the effect of CYP2C19 polymorphism on proton pump inhibition by lansoprazole was investigated using 24-h intragastric pH monitoring in the 32 subjects. Time course of serum lansoprazole concentration following intravenous short infusion was well described by a 2-compartment model. The mean volume of the central and peripheral compartments was 0.110 and 0.201 l/kg, respectively. The mean inter-compartment clearance was estimated to be 0.0882 l/h/kg. The population mean value of systemic clearance in the homoEM (CYP2C19*1/*1), heteroEM (CYP2C19*1/*2 and *1/*3), and PM (CYP2C19*2/*2, *2/*3, and *3/*3) groups was 0.179, 0.109, and 0.038 l/h/kg, respectively. The mean intragastric pH following twice-daily doses of 30 mg lansoprazole was approximately 6, 5, and 4 in the PM, heteroEM, and homoEM groups, respectively. These findings indicate that large interindividual variability exists in the pharmacokinetics of intravenously administered lansoprazole, but that twice-daily infusion of a 30 mg dose leads to significant and sustained proton pump inhibition, even in the homoEM group, despite the short elimination half-life of the drug.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 30 (12), 2238-2243, 2007
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390001204625438208
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- NII Article ID
- 110006546418
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- NII Book ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 9274155
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed