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Titolo:
PHARMACOKINETICS OF SINGLE ORAL AND MULTIPLE INTRAVENOUS AND ORAL-ADMINISTRATION OF ACEBUTOLOL ENANTIOMERS IN A RAT MODEL
Autore:
MOSTAFAVI SA; FOSTER RT;
Indirizzi:
UNIV ALBERTA,FAC PHARM & PHARMACEUT SCI EDMONTON AB T6G 2N8 CANADA UNIV ALBERTA,FAC PHARM & PHARMACEUT SCI EDMONTON AB T6G 2N8 CANADA
Titolo Testata:
Biopharmaceutics & drug disposition
fascicolo: 7, volume: 19, anno: 1998,
pagine: 425 - 431
SICI:
0142-2782(1998)19:7<425:POSOAM>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
CONCENTRATION-TIME PROFILES; BETA-BLOCKER PAFENOLOL; DOUBLE PEAKS; GASTROINTESTINAL ABSORPTION; DISPOSITION; HUMANS; BIOAVAILABILITY; CIMETIDINE;
Keywords:
ACEBUTOLOL ENANTIOMERS; DIACETOLOL; PHARMACOKINETICS; SINGLE; MULTIPLE DOSE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
29
Recensione:
Indirizzi per estratti:
Citazione:
S.A. Mostafavi e R.T. Foster, "PHARMACOKINETICS OF SINGLE ORAL AND MULTIPLE INTRAVENOUS AND ORAL-ADMINISTRATION OF ACEBUTOLOL ENANTIOMERS IN A RAT MODEL", Biopharmaceutics & drug disposition, 19(7), 1998, pp. 425-431

Abstract

Acebutolol (AC), is a chiral, beta-adrenergic blocking agent which possesses partial agonist activity and is metabolized to an equipotent chiral metabolite, diacetolol (DC). The enantiomeric disposition of AC is reported following racemic administration as a single oral (p.o., 50 mg kg(-1)) or as a multiple thrice daily intravenous (i.v.) or p.o. dosing for four days in male Sprague-Dawley rats (n = 6). Enantiomericconcentrations of AC and DC in plasma and urine were determined usinga stereospecific HPLC assay. The bioavailabilities of R- and S-enantiomer were 0.40 and 0.39 after single dose administration of AC respectively. These values were increased to 0.51 and 0.53 after multiple dosing. Although no significant differences were found in AUC(0-infinity)after single i.v. as compared with AUC(0-tau) after multiple i.v. dosing of AC, the 39 and 45% increase in mean AUC(0-tau) were found aftermultiple p.o. dosing over the corresponding AUC(0-infinity), for the single p.o. dose of AC for R- and S-enantiomer, respectively. The disposition of DC as well as the urinary excretion of metabolite was stereoselective in favor of R-enantiomer after oral administration of AC. These results indicate that AC enantiomers have low availability and moderate extraction through the first-pass metabolism in a rat model. The higher AUC values after p.o. multiple dosing may suggest a saturablefirst-pass metabolism of AC. (C) 1998 John Wiley & Sons, Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 22:35:53