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Titolo:
THE EFFECT OF 2,2'-SUBSTITUTION ON THE METABOLISM AND TOXICITY OF DAPSONE IN-VITRO AND IN-VIVO
Autore:
TINGLE MD; MAHMUD R; MAGGS JL; HAWLEY S; COLEMAN MD; WARD SA; PARK BK;
Indirizzi:
UNIV AUCKLAND,SCH MED & HLTH SCI,DEPT PHARMACOL & CLIN PHARMACOL,PRIVATE BAG 92019 AUCKLAND NEW ZEALAND UNIV LIVERPOOL,DEPT PHARMACOL & THERAPEUT LIVERPOOL L69 3BX MERSEYSIDE ENGLAND ASTON UNIV,DEPT PHARMACEUT SCI BIRMINGHAM B4 7ET W MIDLANDS ENGLAND
Titolo Testata:
Environmental toxicology and pharmacology
fascicolo: 2, volume: 5, anno: 1998,
pagine: 145 - 153
SICI:
1382-6689(1998)5:2<145:TEO2OT>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
PNEUMOCYSTIS-CARINII PNEUMONIA; IN-VITRO; GLUCURONOSYLTRANSFERASE; DIPHENYLSULFONES; BIOACTIVATION; HYDROXYLAMINE; INHIBITION; HEMOLYSIS; SULFONES; ENZYMES;
Keywords:
DAPSONE ANALOGS; TOXICITY; 2,2'-SUBSTITUTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
47
Recensione:
Indirizzi per estratti:
Citazione:
M.D. Tingle et al., "THE EFFECT OF 2,2'-SUBSTITUTION ON THE METABOLISM AND TOXICITY OF DAPSONE IN-VITRO AND IN-VIVO", Environmental toxicology and pharmacology, 5(2), 1998, pp. 145-153

Abstract

The effect of 2,2'-substitution with fluorine, methyl or trifluoromethyl groups on the toxicity, metabolism and pharmacological activity ofdapsone has been investigated in vitro and in vivo. There was marked inter-species variation in the bioactivation (N-hydroxylation) of the compounds, as determined by methemoglobin formation. However, the inclusion of fluorine significantly (P < 0.01) reduced methemoglobin formation compared with dapsone in all species studied. All three analogs resulted in significantly (P < 0.001) less methemoglobinemia than dapsone when given either intraperitoneally or intravenously to the male Wistar rat. Rapid plasma clearance of the analogs through increased lipophilicity and enhanced N-glucuronidation may account for the low toxicity compared with dapsone. Although trifluoromethyl substitution resulted in a loss of activity against respiratory burst in human neutrophils in an in vitro model, all three analogs retained pharmacological activity against Plasmodium berghei malaria in an in vivo mouse model. (C) 1998 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/07/20 alle ore 22:34:35