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Titolo:
ENANTIOSELECTIVE HYDROXYLATION OF OMEPRAZOLE CATALYZED BY CYP2C19 IN SWEDISH WHITE SUBJECTS
Autore:
TYBRING G; BOTTIGER Y; WIDEN J; BERTILSSON L;
Indirizzi:
HUDDINGE UNIV HOSP,KAROLINSKA INST,DEPT MED LAB SCI & TECHNOL,DIV CLIN PHARMACOL S-14186 HUDDINGE SWEDEN
Titolo Testata:
Clinical pharmacology and therapeutics
fascicolo: 2, volume: 62, anno: 1997,
pagine: 129 - 137
SICI:
0009-9236(1997)62:2<129:EHOOCB>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFORMANCE LIQUID-CHROMATOGRAPHY; CHIRAL STATIONARY-PHASE; GASTRIC-ACID SECRETION; S-MEPHENYTOIN; SUBSTITUTED BENZIMIDAZOLES; POOR METABOLIZERS; CHINESE SUBJECTS; PLASMA; PHARMACOKINETICS; POLYMORPHISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
34
Recensione:
Indirizzi per estratti:
Citazione:
G. Tybring et al., "ENANTIOSELECTIVE HYDROXYLATION OF OMEPRAZOLE CATALYZED BY CYP2C19 IN SWEDISH WHITE SUBJECTS", Clinical pharmacology and therapeutics, 62(2), 1997, pp. 129-137

Abstract

Stereoselective disposition of omeprazole and its formed 5-hydroxy metabolite were studied in five poor metabolizers and five extensive metabolizers of S-mephenytoin. After a single oral dose of omeprazole (20mg), the plasma concentrations of the separate enantiomers of the parent drug and the 5-hydroxy metabolite were determined for 10 hours after drug intake. In poor metabolizers, the area under the plasma concentration versus time curve [AUC(0-8)] of (+)-omeprazole was larger and that of the 5-hydroxy metabolite of this enantiomer was smaller than the AUC(0-8) values in extensive metabolizers (p < 0.001). The mean AUC(0-8) of the (-)-enantiomer of omeprazole was also higher in poor metabolizers than in extensive metabolizers, but only 3.1-fold compared with 7.5-fold for (+)-omeprazole. The rate of formation of the hydroxy metabolite from (-)-omeprazole was low and not significantly different in poor and extensive metabolizers. These results show that (+)-omeprazole is to a major extent hydroxylated by CYP2C19. Also (-)-omeprazolemay partly be metabolized by this enzyme but is mainly metabolized byanother enzyme, presumably CYP3A4, to the achiral sulfone metabolite. The plasma concentration ratio of omeprazole to 5-hydroxyomeprazole obtained 3 hours after the drug intake has been used to distinguish between extensive and poor metabolizer phenotypes. With use of the ratio between the (+)-enantiomers of the parent drug and the metabolite, a better discrimination between phenotypes was obtained. The ratio between the (-)-enantiomers also separated the phenotypes but mas less discriminatory. For the future, measurement of total concentrations will suffice for phenotyping.

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Documento generato il 25/01/20 alle ore 09:25:45