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  5. Time-dependent amplified pharmacokinetic and pharmacodynamic responses of rabeprazole in cytochrome P450 2C19 poor metabolizers
 
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Time-dependent amplified pharmacokinetic and pharmacodynamic responses of rabeprazole in cytochrome P450 2C19 poor metabolizers

Journal
Pharmacotherapy
Journal Volume
23
Journal Issue
6
Pages
711-719
Date Issued
2003
Author(s)
CHUN-JUNG LIN  
JYH-CHIN YANG  
Uang Y.-S.
Chern H.-D.
Wang T.-H.
DOI
10.1592/phco.23.6.711.32177
URI
https://www.scopus.com/inward/record.uri?eid=2-s2.0-0038689161&doi=10.1592%2fphco.23.6.711.32177&partnerID=40&md5=95959a040518f73c37122d8d93894e6d
https://scholars.lib.ntu.edu.tw/handle/123456789/565083
Abstract
Study Objectives. To determine the pharmacokinetic and pharmacodynamic rationale for the optimum regimen of rabeprazole in the treatment of Helicobacter pylori infection in patients who are cytochrome P450 (CYP) 2C19 poor metabolizers or extensive metabolizers. Design. Prospective, multiple-dose pharmacokinetic and pharmacodynamic study. Setting. University-affiliated medical center in Taiwan. Subjects. Twelve healthy volunteers (aged 20-30 yrs) who were identified as CYP2C19 poor metabolizers (six subjects) or extensive metabolizers (six). Intervention. Each subject received rabeprazole 20 mg twice/day for 3 consecutive days and once/day on the fourth day. Measurements and Main Results. Pharmacokinetic and pharmacodynamic parameters were compared between CYP2C19 poor and extensive metabolizers on day 1 and day 4 of dosing. The mean ± SD values of area under the concentration-time curve of rabeprazole and rabeprazole thioether were significantly higher in poor metabolizers than in extensive metabolizers on day 1 (5357 ± 883 vs 1131 ± 512 ng?hr/ml and 1703 ± 432 vs 561 ± 358 ng?hr/ml, respectively; p<0.001) and on day 4 (5601 ± 669 vs 1619 ± 778 ng?hr/ml and 1914 ± 378 vs 511 ± 360 ng?hr/ml, respectively; p<0.001). However, no significant difference was noted between day 1 and day 4 of dosing within the same genotype groups. Only CYP2C19 poor metabolizers had significantly higher plasma gastrin levels on day 4 compared with those levels on day 1 (p<0.05). The pharmacokinetic-pharmacodynamic relationship of rabeprazole appears to be time dependent. Conclusion. The pharmacokinetic and pharmacodynamic data suggest that CYP2C19 poor metabolizers might be subject to advantageous conditions, especially after day 4, for treating H. pylori infection with rabeprazole.
SDGs

[SDGs]SDG3

Other Subjects
cytochrome P450 2C19; gastrin; rabeprazole; rabeprazole thioether; unclassified drug; adult; area under the curve; article; concentration response; controlled study; dose time effect relation; drug metabolism; female; gastrin blood level; genotype; Helicobacter infection; Helicobacter pylori; human; human experiment; male; multiple drug dose; normal human; pharmacodynamics; prospective study; Taiwan; 2-Pyridinylmethylsulfinylbenzimidazoles; Academic Medical Centers; Adult; Aryl Hydrocarbon Hydroxylases; Benzimidazoles; Breath Tests; Female; Gastrins; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metabolic Detoxication, Drug; Mixed Function Oxygenases; Omeprazole; Prospective Studies; Proton Pumps; Taiwan; Time Factors
Type
journal article

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