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Titolo:
COMPARISON OF 3 CYP2D6 PROBE SUBSTRATES AND GENOTYPE IN GHANAIANS, CHINESE AND CAUCASIANS
Autore:
DROLL K; BRUCEMENSAH K; OTTON SV; GAEDIGK A; SELLERS EM; TYNDALE RF;
Indirizzi:
UNIV TORONTO,DEPT PHARMACOL,1 KINGS COLL CIRCLE TORONTO ON M5S 1A8 CANADA UNIV TORONTO,DEPT PHARMACOL TORONTO ON M5S 1A8 CANADA ADDICT RES FDN TORONTO ON CANADA UNIV TORONTO,DEPT PSYCHIAT TORONTO ON CANADA CHILDRENS MERCY HOSP KANSAS CITY MO 00000 UNIV TORONTO,DEPT MED TORONTO ON CANADA UNIV TORONTO,CTR RES WOMENS HLTH TORONTO ON CANADA
Titolo Testata:
Pharmacogenetics
fascicolo: 4, volume: 8, anno: 1998,
pagine: 325 - 333
SICI:
0960-314X(1998)8:4<325:CO3CPS>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEBRISOQUINE HYDROXYLATION; SPARTEINE OXIDATION; POOR METABOLIZERS; GENETIC-ANALYSIS; NATIVE CHINESE; POPULATION; MEPHENYTOIN; INHIBITION; QUINIDINE; POLYMORPHISMS;
Keywords:
DEXTROMETHORPHAN; CYTOCHROME P450; CYP2D6; SPARTEINE; DEBRISOQUINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
33
Recensione:
Indirizzi per estratti:
Citazione:
K. Droll et al., "COMPARISON OF 3 CYP2D6 PROBE SUBSTRATES AND GENOTYPE IN GHANAIANS, CHINESE AND CAUCASIANS", Pharmacogenetics, 8(4), 1998, pp. 325-333

Abstract

The ability to metabolize CYP2D6 substrates sparteine, debrisoquine, and dextromethorphan was studied in healthy Caucasian (n = 20), Ghanaian (n = 21), and Chinese (n = 22) CYP2D6 extensive metabolizers. Genotype analysis for the CYP2D61, *3, *4, *5, *9, *10, and *17 alleles was performed. Interethnic differences in the disposition of the probe drugs were found among the extensive metabolizers; extensive metabolizer status was confirmed by phenotype and genotype analysis. The mean metabolic rate was lower for Caucasians than for Ghanaians for sparteine(P < 0.02) and for both Ghanaians and Chinese for debrisoquine (P < 0.02). Correlation comparisons resulted in lower pairwise correlation coefficients in Ghanaians compared with Chinese and Caucasians for every combination of probe substrates. In addition, in Chinese and Caucasians, metabolic rates for each pair of probe drugs were significantly correlated (P < 0.002), but in Ghanaians the dextromethorphan metabolicrates were not correlated to either sparteine or debrisoquine (P < 0.05), Even when only those with a CYP2D61/*1 genotype were included inthe correlation calculations, the Ghanaians had very low correlation coefficients (r(s) - 0.02-0.2, n = 9); much lower than those found in Caucasian (r(s) 0.78-0.92, n = 14) or Chinese (r(s) 0.54-0.96, n = 7) individuals. Quinidine had significantly less affect on sparteine metabolic rates in Ghanaians than both Caucasians and Chinese (P < 0.02). In addition, five of the 21 Ghanaian individuals had dextromethorphan metabolic ratios which were unaffected by quinidine. These individualsalso had differences in urinary recovery of dextromethorlphan and itsmetabolites when compared to the other Ghanaian individuals. These results confirm the large ethnic differences in probe drug metabolism and quinidine sensitivity among these ethnic groups. They also suggest that the Ghanaians have an additional unidentified allele(s) with altered substrate specificity and quinidine sensitivity which is currently genotyped as CYP2D61. Pharmacogenetics 8:325-333 (C) 1938 Lippincott-Raven Publishers.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 06:23:32