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Titolo:
COVALENT BINDING OF CARBAMAZEPINE REACTIVE METABOLITES TO P450 ISOFORMS PRESENT IN THE SKIN
Autore:
WOLKENSTEIN P; TAN C; LECOEUR S; WECHSLER J; GARCIAMARTIN N; CHARUE D; BAGOT M; BEAUNE P;
Indirizzi:
UNIV PARIS 12,CHU HENRI MONDOR,DEPT DERMATOL F-94010 CRETEIL FRANCE CHU NECKER ENFANTS MALAD,INSERM,U75 F-75730 PARIS FRANCE UNIV PARIS 12,CHU HENRI MONDOR,DEPT PATHOL F-94010 CRETEIL FRANCE
Titolo Testata:
Chemico-biological interactions
fascicolo: 1, volume: 113, anno: 1998,
pagine: 39 - 50
SICI:
0009-2797(1998)113:1<39:CBOCRM>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
TOXIC EPIDERMAL NECROLYSIS; MOUSE-LIVER MICROSOMES; MONOCLONAL-ANTIBODIES; HUMAN KERATINOCYTES; TIENILIC ACID; DRUG; CYTOCHROME-P-450; PROTEINS; ENZYMES; BIOACTIVATION;
Keywords:
CARBAMAZEPINE; CYTOCHROME P450 3A4; CYTOCHROME P450 1A2; REACTIVE METABOLITES; SKIN; HYPERSENSITIVITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
30
Recensione:
Indirizzi per estratti:
Citazione:
P. Wolkenstein et al., "COVALENT BINDING OF CARBAMAZEPINE REACTIVE METABOLITES TO P450 ISOFORMS PRESENT IN THE SKIN", Chemico-biological interactions, 113(1), 1998, pp. 39-50

Abstract

Carbamazepine is an anticonvulsant associated with a high risk for severe cutaneous reactions. Upon metabolism by cytochrome P450, carbamazepine may produce reactive metabolites. We evaluated in vitro the covalent binding of carbamazepine reactive metabolites on human P450s and then the presence of these P450s in human epidermis. Carbamazepine reactive metabolites covalent binding to human liver microsomes involved P450 subfamilies 1A, 2C and 3A. Specific covalent binding to yeasts expressing different P450s showed that carbamazepine reactive metabolites bound specifically to P450 1A2 and 3A4. We confirmed the constitutive presence of P450 3A in human epidermis and after induction with coaltar of P450 IA. Consequently, the production in epidermis of carbamazepine reactive metabolites is theoretically possible with formation of P450 adduct metabolites. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 04:00:11