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Titolo:
PHARMACOKINETICS OF A NEW THIENODIAZEPINE PLATELET-ACTIVATING-FACTOR RECEPTOR ANTAGONIST (E6123) IN LABORATORY-ANIMALS - IS THERE A METABOLIC POLYMORPHISM IN THE RHESUS-MONKEY
Autore:
KUSANO K; TANAKA 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:
Xenobiotica
fascicolo: 6, volume: 23, anno: 1993,
pagine: 589 - 598
SICI:
0049-8254(1993)23:6<589:POANTP>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
OXIDATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
15
Recensione:
Indirizzi per estratti:
Citazione:
K. Kusano et al., "PHARMACOKINETICS OF A NEW THIENODIAZEPINE PLATELET-ACTIVATING-FACTOR RECEPTOR ANTAGONIST (E6123) IN LABORATORY-ANIMALS - IS THERE A METABOLIC POLYMORPHISM IN THE RHESUS-MONKEY", Xenobiotica, 23(6), 1993, pp. 589-598

Abstract

1. The pharmacokinetics of E6123, a platelet activating factor receptor antagonist,were studied after i.v. and oral administration to rat, guinea-pig, dog and rhesus monkey. Plasma concentrations of E6123 weredetermined by h.p.l.c. with UV detection. 2. After i.v. dosing (I mg/kg), the plasma concentration-time curves fitted a two-compartment model. The half-lives for the terminal phases (t1/2) in rat, dog, and guinea-pig showed very little inter-individual variation, but t1/2 in themonkey (n = 4) varied more than four-fold. The distribution parameters were very similar in rat, dog and monkey (V(c) and V(ss) approx. 1.2and 1.5 l/kg, respectively) but slightly higher values were found in the guinea-pig, which also showed the lowest plasma protein binding. 3. After oral dosing (1 mg/kg), the maximum plasma concentrations were obtained within 0.3-3.0 h in all species. The half-life for each individual animal was almost the same as that after i.v. dosing. The mean bioavailabilities of E6123 in rat, guinea-pig and dog were about 65, 95and 81%, respectively, but the values for monkey were again highly variable (range 32-99%). 4. The high variability in the monkey was confirmed by i.v. administration to a further 10 animals. The mean half-lives for the terminal phase in extensive metabolizers (EMs) (n = 4) and poor metabolizers (PMs) (n = 10) were approx. 1 and 4h, respectively. 5. The rank order for total body clearance of E6123 was: rat > monkey (EMs) > dog > guinea-pig > monkey (PMs).

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 10:35:40