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Titolo:
DETERMINATION OF DEXTROMETHORPHAN METABOLIC PHENOTYPE BY SALIVARY ANALYSIS WITH A REFERENCE TO GENOTYPE IN CHINESE PATIENTS RECEIVING RENALHEMODIALYSIS
Autore:
HOU ZY; CHEN CP; YANG WC; LAI MD; BUCHERT ET; CHUNG HM; PICKLE LW; WOOSLEY RL;
Indirizzi:
GODS HELP HOSP,DEPT MED,66 LANE 601 SECT 2,PEI KANG RD TAI PAO CHIA YI CTY TAIWAN VET GEN HOSP,DEPT MED KAOHSIUNG TAIWAN NATL CHENG KUNG UNIV,COLL MED,DEPT BIOCHEM TAINAN TAIWAN GEORGETOWN UNIV,MED CTR,DEPT PHARMACOL WASHINGTON DC 20007 CTR DIS CONTROL,NATL CTR HLTH STAT,US DEPT HHS ATLANTA GA 30333
Titolo Testata:
Clinical pharmacology and therapeutics
fascicolo: 4, volume: 59, anno: 1996,
pagine: 411 - 417
SICI:
0009-9236(1996)59:4<411:DODMPB>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
COMMON GENETIC-DEFECT; DEBRISOQUINE HYDROXYLATION; POOR METABOLIZERS; POLYMORPHISM; OXIDATION; SPARTEINE; QUINIDINE; DISPOSITION; CYP2D6; INHIBITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
27
Recensione:
Indirizzi per estratti:
Citazione:
Z.Y. Hou et al., "DETERMINATION OF DEXTROMETHORPHAN METABOLIC PHENOTYPE BY SALIVARY ANALYSIS WITH A REFERENCE TO GENOTYPE IN CHINESE PATIENTS RECEIVING RENALHEMODIALYSIS", Clinical pharmacology and therapeutics, 59(4), 1996, pp. 411-417

Abstract

Background: The polymorphic metabolism of debrisoquin and sparteine by cytochrome P450IID6 (CYP2D6) is genetically determined. Determination of the CYP2D6 metabolic phenotype with conventional urine analytic methods is not feasible in anuric patients with renal failure. The possibility of using salivary analysis, with dextromethorphan as a probe drug, to determine the CYP2D6 metabolic phenotype in patients with renal failure was evaluated. Methods and results: One hundred four Chinesepatients with renal failure were recruited. All 104 patients were receiving hemodialysis. Saliva was collected before and at 3 hours after each patient took a capsule of dextromethorphan hydrobromide (30 mg). Four patients were excluded because of insufficient samples of saliva. The distribution of logarithms of the metabolic ratios (log[MR]) in the 100 patients appeared to be: normal. Administration of quinidine sulfate (200 mg twice daily) to nine of the, patients significantly and markedly increased the dextromethorphan metabolic ratios. The metabolic ratios of nine patients pretreated with quinidine were higher than any of the 100 patients with renal failure who did not receive quinidine pretreatment. A metabolic ratio of 33 separated these two groups. Genomic deoxyribonucleic acid was extracted from whole blood in a. subset of patients. Polymerase chain reaction (PCR)-based methods were usedto detect the CYP2D6 and B mutant genes. Mutant B alleles (which are common in white poor metabolizers) of CYP2D6 genes were not detected in any of the 47 subjects tested. A PCR-based test of cytosine (C-188) to thymine (T-188) polymorphism at 188 base pairs in exon 1 of CYP2D6 genes was performed in 61 patients. Subjects who were homozygous for C-188 had significantly (p = 0.0067) lower log[MR] values than those who were homozygous for T-188. Conclusions: Determination of dextromethorphan metabolic ratios in saliva is feasible in patients with renal failure requiring hemodialysis. All subjects in this study appeared to be ''extensive metabolizer'' phenotype for CYP2D6, and no poor metabolizer was identified. From the results with quinidine pretreatment, a metabolic ratio of 33 is suggested to be a tentative antimode for identification of poor metabolizers in patients with renal failure.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 09:59:48