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Titolo:
BIOACTIVATION AND BIOINACTIVATION OF DRUGS AND DRUG METABOLITES - RELEVANCE TO ADVERSE DRUG-REACTIONS
Autore:
PARK BK; PIRMOHAMED M; TINGLE MD; MADDEN S; KITTERINGHAM NR;
Indirizzi:
UNIV LIVERPOOL,DEPT PHARMACOL & THERAPEUT,POB 147 LIVERPOOL L69 3BX MERSEYSIDE ENGLAND
Titolo Testata:
Toxicology in vitro
fascicolo: 4, volume: 8, anno: 1994,
pagine: 613 - 621
SICI:
0887-2333(1994)8:4<613:BABODA>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN LIVER-MICROSOMES; ALZHEIMERS-DISEASE; CARBAMAZEPINE-HYPERSENSITIVITY; N-HYDROXYLATION; IN-VITRO; AMODIAQUINE; DAPSONE; RAT; PROTEIN; INVITRO;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
43
Recensione:
Indirizzi per estratti:
Citazione:
B.K. Park et al., "BIOACTIVATION AND BIOINACTIVATION OF DRUGS AND DRUG METABOLITES - RELEVANCE TO ADVERSE DRUG-REACTIONS", Toxicology in vitro, 8(4), 1994, pp. 613-621

Abstract

Adverse drug reactions that cannot be predicted from the pharmacological properties of the drug and which are not easily reproduced in laboratory animals are a major complication of drug therapy. It is necessary to investigate the mechanisms of such reactions in order to (1) define structural features within a given drug molecule which are responsible for causing toxicity and (2) to identify those individuals who are particularly sensitive to a given drug reaction. In theory, drug toxicity may arise by direct toxicity, genotoxicity or immune-mediated toxicity caused by either parent drug or chemical. In this respect chemically reactive metabolites are of particular importance and the balance between bioactivation and bioinactivation pathways of drug metabolism will be a critical factor in both the type and extent of toxicity. We have therefore developed in vitro techniques that incorporate human cells for the detection and characterization of stable, chemically reactive and cytotoxic metabolites. In such experiments bioactivation (byCYP1A, CYP2D6, CYP3A, etc.) can be investigated by use of a liver bank, while lymphocytes provide accessible human cells, which can be obtained from both patients and volunteers, genotyped and/or phenotyped for particular drug-metabolizing enzymes (eg. glutathione transferase mu). The relevance of in vitro experiments to drug toxicity observed in humans will be illustrated by reference to studies with anticonvulsants and antimalarials.

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Documento generato il 02/07/20 alle ore 21:56:28