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Titolo:
CYP2C19 GENOTYPE AND PHENOTYPE DETERMINED WITH OMEPRAZOLE IN PATIENTSWITH ACID-RELATED DISORDERS WITH AND WITHOUT HELICOBACTER-PYLORI INFECTION
Autore:
SAGAR M; SEENSALU R; TYBRING G; DAHL ML; BERTILSSON L;
Indirizzi:
HUDDINGE UNIV HOSP,KAROLINSKA INST,DEPT CLIN PHARMACOL S-14186 HUDDINGE SWEDEN HUDDINGE UNIV HOSP,DEPT SURG,KAROLINSKA INST,CLIN RES CTR S-14186 HUDDINGE SWEDEN HUDDINGE UNIV HOSP,DEPT MED,KAROLINSKA INST,CLIN RES CTR S-14186 HUDDINGE SWEDEN HUDDINGE UNIV HOSP,DEPT MED LAB SCI & TECHNOL,KAROLINSKA INST,DIV CLIN PHARMACOL S-14186 HUDDINGE SWEDEN
Titolo Testata:
Scandinavian journal of gastroenterology
fascicolo: 10, volume: 33, anno: 1998,
pagine: 1034 - 1038
SICI:
0036-5521(1998)33:10<1034:CGAPDW>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
S-MEPHENYTOIN; POOR METABOLIZERS; HYDROXYLATION; POLYMORPHISM; POPULATIONS; PHARMACOKINETICS; DEBRISOQUIN; JAPANESE; CHINESE; WHITE;
Keywords:
CYP2C19; GENOTYPE; HELICOBACTER PYLORI; PHENOTYPE; OMEPRAZOLE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
26
Recensione:
Indirizzi per estratti:
Citazione:
M. Sagar et al., "CYP2C19 GENOTYPE AND PHENOTYPE DETERMINED WITH OMEPRAZOLE IN PATIENTSWITH ACID-RELATED DISORDERS WITH AND WITHOUT HELICOBACTER-PYLORI INFECTION", Scandinavian journal of gastroenterology, 33(10), 1998, pp. 1034-1038

Abstract

Background: Omeprazole is to a major extent metabolized by cytochromeP450 isozyme CYP2C19. The aims of this study were to compare the phenotype of CYP2C19 determined by omeprazole with the genotype and to determine the effect of Helicobacter pylori infection on the metabolism of omeprazole. Methods: One-hundred and forty-three Caucasian patients with acid-related disorders assessed with a combination of gastrointestinal symptoms and upper endoscopic findings were given 20 mg omeprazole orally. Three hours after intake, omeprazole and 5-hydroxyomeprazole plasma concentrations were determined with high-performance liquid chromatography, and the phenotype for metabolic capacity was expressed as metabolic ratio (MR). Genotyping of defect alleles (CYP2C192 and *3) was performed by polymerase chain reaction amplification. One hundred eleven patients were tested after the first dose of omeprazole and 32 patients after repetitive administration (median time, 30 days). H.pylori serology was determined with enzyme-linked immunosorbent assayat the time of phenotyping. Results: Genotypically, 2.8% had two mutated alleles and were poor metabolizers (PM), and 22.4% were heterozygous extensive metabolizers (EM). Among the 111 patients who received the first omeprazole dose, 4 patients had MR >5-that is, belonged to thePM phenotype. Two of these had PM genotype (both CYP2C192/*2), and two had an EM genotype (CYP2C191/*1 and *1/*3), indicating that they have still unidentified mutations. In the heterozygous EM group the mean MR was higher in patients who had been on continued omeprazole treatment than in those given the first dose (5.7 versus 2.5, P = 0.02). There were no significant differences in MR and omeprazole concentrations between H, pylori-negative (43%) and -positive (57%) patients. Conclusion: In all but two patients with probable unidentified mutations there was agreement between the CYP2C19 phenotype determined by omeprazole and the genotype. The metabolism of omeprazole in patients with acid-related disorders is genetically determined and without relation to H. pylori infection.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/01/20 alle ore 14:48:09