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Titolo:
COMPARISON OF CYP2A6 CATALYTIC ACTIVITY ON COUMARIN 7-HYDROXYLATION IN HUMAN AND MONKEY LIVER-MICROSOMES
Autore:
LI Y; LI NY; SELLERS EM;
Indirizzi:
UNIV TORONTO,DEPT PHARMACOL,ROOM 4334,MED SCI BLDG,1 KINGS COLL CIRCLE TORONTO ON M5S 1A8 CANADA UNIV TORONTO,DEPT PHARMACOL TORONTO ON M5S 1A8 CANADA UNIV TORONTO,DEPT MED TORONTO ON M5S 1A8 CANADA UNIV TORONTO,DEPT PSYCHIAT TORONTO ON M5S 1A8 CANADA WOMENS COLL HOSP,CTR RES WOMENS HLTH,PSYCHOPHARMACOL & DEPENDENCE RESUNIT TORONTO ON M5S 1B2 CANADA ADDICT RES FDN TORONTO ON M5S 2S1 CANADA
Titolo Testata:
European journal of drug metabolism and pharmacokinetics
fascicolo: 4, volume: 22, anno: 1997,
pagine: 295 - 304
SICI:
0378-7966(1997)22:4<295:COCCAO>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
SPECIES-DIFFERENCES; CYNOMOLGUS MONKEY; RHESUS-MONKEY; PHASE-I; METABOLISM; MOUSE; CYTOCHROME-P450; PURIFICATION; INHIBITION; RAT;
Keywords:
CYP2A6; MONKEY; HUMAN; MICROSOMES; COUMARIN 7-HYDROXYLATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
26
Recensione:
Indirizzi per estratti:
Citazione:
Y. Li et al., "COMPARISON OF CYP2A6 CATALYTIC ACTIVITY ON COUMARIN 7-HYDROXYLATION IN HUMAN AND MONKEY LIVER-MICROSOMES", European journal of drug metabolism and pharmacokinetics, 22(4), 1997, pp. 295-304

Abstract

Comparison of 7-hydroxylation of coumarin, a CYP2A6 substrate, in human and African green and cynomolgus monkey liver microsomes was made by means of an HPLC assay with UV detection. In human liver microsomes,the K-m and V-max values for the metabolic conversion were 2.1 mu M and 0.79 nmol/mg/min, respectively. While African green monkey showed K-m and V-max values of 2.7 mu M and 0.52 nmol/mg/min, which were similar to human, higher K-m and V-max values were found in cynomolgus monkey. Coumarin 7-hydroxylation in human and African green monkey was selectively inhibited by methoxsalen and pilocarpine (CYP2A6 inhibitors) but not by other inhibitors, i.e. alpha-naphthoflavone (CYP1A1), orphenadrine (CYP2B6), sulfaphenazole (CYP2C9), quinidine (CYP2D6) and ketoconazole (CYP3A4). Immunoinhibition results supported CYP2A6 involvement in human and its homolog in monkey in coumarin 7-hydroxylation, as only anti-CYP2A6, but not CYP2B1, CYP2C13, CYP2D6, CYP2E1 or CYP3A antibodies, inhibited this conversion. African green monkey was found to be similar to human in catalytic activity of coumarin 7-hydroxylation and response to CYP2A6 inhibitors or antibody inhibition: However, themonkey CYP2A6 is not identical to the human in that K-i values were different, and differences were observed with some CYP2A6 inhibitors, such as nicotine and methoxsalen, suggesting that, under some circumstances, studies of nicotine kinetics and drug taking behavior in monkey may not be comparable to human.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/08/20 alle ore 00:22:29