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Titolo:
DISPOSITION OF SALMETEROL XINAFOATE IN LABORATORY-ANIMALS AND HUMANS
Autore:
MANCHEE GR; BARROW A; KULKARNI S; PALMER E; OXFORD J; COLTHUP PV; MACONOCHIE JG; TARBIT MH;
Indirizzi:
GLAXO GRP RES LTD,DEPT DRUG METAB 3,PK RD WARE SG12 0DP HERTS ENGLAND
Titolo Testata:
Drug metabolism and disposition
fascicolo: 6, volume: 21, anno: 1993,
pagine: 1022 - 1028
SICI:
0090-9556(1993)21:6<1022:DOSXIL>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
11
Recensione:
Indirizzi per estratti:
Citazione:
G.R. Manchee et al., "DISPOSITION OF SALMETEROL XINAFOATE IN LABORATORY-ANIMALS AND HUMANS", Drug metabolism and disposition, 21(6), 1993, pp. 1022-1028

Abstract

The disposition of [C-14]salmeterol xinafoate, a new inhaled beta2-adrenoceptor agonist with both bronchodilator and antiinflammatory activity, has been studied in laboratory animals and humans following intravenous and oral administration. [C-14]Salmeterol was rapidly absorbed in animal species and humans with C(max) observed within 2 hr. C(max) was similar for normalized oral dose level in mice, rats, and rabbits. In dogs, C(max) was higher and reflected the greater oral bioavailability in this species. The plasma t1/2, after intravenous administration, was 5 hr in rats and 2 hr in dogs. The volume of distribution of salmeterol was significantly greater than total body water in both rats (40 liters/kg) and dogs (6 liters/kg) and indicated high tissue uptakeof the compound. Plasma clearance was high in rats (95 ml/min/kg) anddogs (30 ml/min/kg). Radioactive drug-related material was widely distributed throughout body tissues in rats. The highest concentrations were present in kidney, liver, gastrointestinal tract, pituitary, lung,heart, and bone marrow. Transfer of radioactive drug-related Materialacross the placental barrier or into milk, studied in rats, was low. In all species the majority of an oral or intravenous dose (55-75%) was excreted in feces. Biliary excretion in rats and dogs accounted for 53% (0-27 hr) and 40% (0-8 hr) of an oral dose, respectively, indicating good absorption across the gastrointestinal tract. Enterohepatic circulation was significant in rats. Salmeterol was cleared predominantly by metabolism in animals and humans. The major routes of metabolism were species-dependent, such that in mice, rats, and rabbits, glucuronidation of parent compound was predominant, in dog phase I metabolism followed by sulfation was the major route, and in humans aliphatic oxidation was predominant.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/03/20 alle ore 23:30:08