Document Detail


Determination of dextromethorphan metabolic phenotype by salivary analysis with a reference to genotype in Chinese patients receiving renal hemodialysis.
MedLine Citation:
PMID:  8612385     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 Chinese patients 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 used to 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 (C188) to thymine (T188) polymorphism at 188 base pairs in exon 1 of CYP2D6 genes was performed in 61 patients. Subjects who were homozygous for C188 had significantly (p = 0.0067) lower log[MR] values than those who were homozygous for T188. 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.
Authors:
Z Y Hou; C P Chen; W C Yang; M D Lai; E T Buchert; H M Chung; L W Pickle; R L Woosley
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  59     ISSN:  0009-9236     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  1996 Apr 
Date Detail:
Created Date:  1996-06-05     Completed Date:  1996-06-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  411-7     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Veterans General Hospital, Kaohsiung, Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Adult
Anti-Arrhythmia Agents / pharmacology
China / ethnology
Cytochrome P-450 CYP2D6
Cytochrome P-450 Enzyme System
Dextromethorphan / pharmacokinetics*
Female
Genotype
Humans
Kidney Failure, Chronic / metabolism*,  therapy
Male
Middle Aged
Mixed Function Oxygenases
Phenotype
Quinidine / pharmacology
Renal Dialysis*
Saliva / metabolism*
Taiwan
Chemical
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 125-71-3/Dextromethorphan; 56-54-2/Quinidine; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.-/Mixed Function Oxygenases; EC 1.14.14.1/Cytochrome P-450 CYP2D6

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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