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Titolo:
DEVELOPMENT OF RADIOIMMUNOASSAY FOR THE NOVEL PLATELET-ACTIVATING-FACTOR RECEPTOR ANTAGONIST, E6123, AND ITS APPLICATION TO PHARMACOKINETICS IN LABORATORY-ANIMALS
Autore:
KUSANO K; TADANO K; TANAKA S; KAGEI Y; UEDA M; MIYAZAWA S; ABE Y; IDA S; YUZURIHA T;
Indirizzi:
EISAI & CO LTD,TSUKUBA RES LABS,1-3 TOKODAI 5-CHOME TSUKUBA IBARAKI 30026 JAPAN
Titolo Testata:
Biological & pharmaceutical bulletin
fascicolo: 2, volume: 17, anno: 1994,
pagine: 334 - 339
SICI:
0918-6158(1994)17:2<334:DORFTN>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
GUINEA-PIGS;
Keywords:
RADIOIMMUNOASSAY; PHARMACOKINETICS; LABORATORY ANIMAL; E6123;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
13
Recensione:
Indirizzi per estratti:
Citazione:
K. Kusano et al., "DEVELOPMENT OF RADIOIMMUNOASSAY FOR THE NOVEL PLATELET-ACTIVATING-FACTOR RECEPTOR ANTAGONIST, E6123, AND ITS APPLICATION TO PHARMACOKINETICS IN LABORATORY-ANIMALS", Biological & pharmaceutical bulletin, 17(2), 1994, pp. 334-339

Abstract

A direct radioimmunoassay for the determination of E6123, a novel antagonist of platelet activating factor (PAF) receptor, was developed inorder to study the pharmacokinetics at low dose. This procedure used [H-3]E6123 as the radioligand and an antiserum obtained from rabbits immunized with the hapten covalently bound to bovine serum albumin. M1B, one of the main metabolites of E6123, exhibited cross-reactivity with antisera. But this metabolite had no effect on measurements of E6123, because the amount of M1B in plasma radioactivity after administration of [C-14]E6123 to dogs and monkeys was low. The sensitivity limit of this assay was 25 pg/ml of plasma when 0.1 ml of plasma was used andthe assay showed good accuracy and high precision. The validity of the radioimmunoassay was demonstrated by comparative analysis of a number of samples after oral and intravenous administration (1.0 mg/kg) by HPLC-UV method (r = 0.972-0.984, slope = 1.0314-1.2143). The pharmacokinetics of E6123 was studied at a dose of 30 mu g/kg. After intravenous administration, the plasma concentration-time curves in all species fitted a two-compartment model and the terminal half-lives in guinea pigs, dogs and monkeys (both poor and extensive metabolizers) were 4.77, 1.71, 5.34 and 1.07 h, respectively. After oral administration, the maximum plasma concentrations were obtained within 0.83-3.00 h and thehalf-life for each animal was almost the same as that after intravenous administration. The mean bioavailabilities of E6123 in guinea pigs,dogs and monkeys (poor and extensive metabolizers) were 106.9, 45.7, 59.1 and 22.8%, respectively.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 17/01/20 alle ore 20:14:35