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Titolo:
A discordance of the cytochrome P4502C19 genotype and phenotype in patients with advanced cancer
Autore:
Williams, ML; Bhargava, P; Cherrouk, I; Marshall, JL; Flockhart, DA; Wainer, IW;
Indirizzi:
Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 armacol, Washington, DC 20007 USA Georgetown Univ, Lombardi Canc Ctr, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 anc Ctr, Washington, DC 20007 USA
Titolo Testata:
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
fascicolo: 5, volume: 49, anno: 2000,
pagine: 485 - 488
SICI:
0306-5251(200005)49:5<485:ADOTCP>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
OMEPRAZOLE; METABOLISM; CYP2C19; IDENTIFICATION; HYDROXYLATION; MECHANISMS; CACHEXIA;
Keywords:
advanced cancer patients; CYP2C19; genotype; phenotype;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
15
Recensione:
Indirizzi per estratti:
Indirizzo: Wainer, IW Georgetown Univ, Med Ctr, Dept Pharmacol, Rm C305,Med Dent Bldg,3900 Reservoir Rd NW, Washington, DC 20007 USA Georgetown Univ Rm C305,MedDent Bldg,3900 Reservoir Rd NW Washington DC USA 20007
Citazione:
M.L. Williams et al., "A discordance of the cytochrome P4502C19 genotype and phenotype in patients with advanced cancer", BR J CL PH, 49(5), 2000, pp. 485-488

Abstract

Aims To examine the relationship between cytochrome P450 2C19 (CYP2C19) genotype and expressed metabolic activity in 16 patients with advanced metastatic cancer. Methods Individual CYP2C19 genotypes were determined by PCR-based amplification, followed by restriction fragment length analysis, and compared with observed CYP2C19 metabolic activity, as determined using the log hydroxylation index of omeprazole. Results All 16 patients had an extensive metabolizer genotype. However, based on the antimode in a distribution of log omeprazole hydroxylation indices h-om healthy volunteers, four of the patients had a poor metabolizer phenotype and there was a general shift of the remaining 12 patients towards aslower metabolic phenotype. This suggests a reduction in metabolic activity for all patients relative to healthy volunteers. A careful analysis of patient medical records failed to reveal any drug interactions or other source for the observed discordance between genotype and phenotype. Conclusions There are no previous reports of a 'discordance' between genotype and expressed enzyme activity in cancer patients. Such a decrease in enzyme activity could have an impact on the efficacy and toxicity of chemotherapeutic agents and other drugs, used in standard oncology practice.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 15:40:17