본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Determination of dextromethorphan metabolic phenotype by salivary analysis with a reference to genotype in Chinese patients receiving renal hemodialysis.

Hou, Z Y ; Chen, C P ; Yang, W C ; Lai, M D ; Buchert, E T ; Chung, H M ; Pickle, L W ; Woosley, R L ;
  • 초록  

    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.


 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
  • 원문이 없습니다.
유료다운로드
  • American Society for Clinical Pharmacology and Therapeutics : 저널

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기