Autor(en): Ahmad, Lateef
Iqbal, Zafar
Nazir, Shabnam
Khan, Abad
Shah, Yasar
Khan, Muhammad Imran
Khan, Ismail
Khan, Amjad
Titel: Effect of clopidogrel on the hydroxylation and sulfoxidation of omeprazole
Sonstige Titel: a single dose study in healthy human volunteers
Sprache (ISO): en
Zusammenfassung: Based upon the known potential interaction between omeprazole (OMP) and clopidogrel (CLOP), the current study was designed to evaluate the effect of CLOP on disposition of OMP and its two major metabolites, 5-hy- droxyomeprazole (5-OH-OMP) and omeprazole sulfone (OMP-S) in healthy clinical subjects. A randomized, open label, 2-period, crossover study was designed. Twelve volunteers were selected, of whom eight were extensive metabolizers (EM) of CYP2C19 and 4 were poor metabolizers (PM). They received single dose of OMP either alone or in combination with CLOP (single dose) and samples were collected periodically to calculate various pharmacokinetic parameters. Changes in most of the pharmacokinetic parameters of OMP, 5-OH-OMP and OMP- S were insignificant (P ˃ 0.05) both in EM and PM except for the maximum concentration (Cmax) of 5-OH-OMP and OMP-S in EM. The OMP Cmax and AUC0-∞ was increased both in EM and PM after concomitant administration of OMP with CLOP. The 5-OH-OMP Cmax was decreased in both EM and PM, demonstrating that CLOP inhibits hydroxylation of OMP. The OMP-S Cmax and AUC0-∞ were increased both in EM and PM showing that CLOP may induce sulfoxidation of OMP. It was concluded that CLOP may inhibit hydroxylation of OMP to a greater extent in EM than in PM, leading to higher OMP Cmax and AUC0-∞. Furthermore, the sulfoxidation of OMP may also be induced by CLOP. So, it is suggested that both these drugs should be carefull prescribed together to avoid any harm to the patients. (Application number13/EC/Pharm. Ref number 12/Pharm).
Schlagwörter: Clopidogrel
Omeprazole
Drug interactions
Pharmacokinetics
Poor metabolizers
Extensive metabolizers
URI: http://hdl.handle.net/2003/36104
http://dx.doi.org/10.17877/DE290R-18120
Erscheinungsdatum: 2017-03-22
Rechte (Link): http://creativecommons.org/licenses/by/4.0/
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