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Titolo:
DISPOSITION OF SUMATRIPTAN IN LABORATORY-ANIMALS AND HUMANS
Autore:
DIXON CM; SAYNOR DA; ANDREW PD; OXFORD J; BRADBURY A; TARBIT MH;
Indirizzi:
GLAXO GRP RES LTD,DEPT DRUG METAB 3 WARE SG12 0DP HERTS ENGLAND
Titolo Testata:
Drug metabolism and disposition
fascicolo: 5, volume: 21, anno: 1993,
pagine: 761 - 769
SICI:
0090-9556(1993)21:5<761:DOSILA>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
GR43175; DOG;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
15
Recensione:
Indirizzi per estratti:
Citazione:
C.M. Dixon et al., "DISPOSITION OF SUMATRIPTAN IN LABORATORY-ANIMALS AND HUMANS", Drug metabolism and disposition, 21(5), 1993, pp. 761-769

Abstract

Sumatriptan is a new 5HT1-like agonist that has proved a novel and effective treatment for migraine. The disposition of the C-14-radiolabeled drug in laboratory animals and humans after oral and parenteral administration is described. Oral absorption of sumatriptan is essentially complete in dogs and rabbits, but only approximately 50% in rat. In humans, at least 57% of an oral dose is absorbed. Bioavailabilities are species dependent (14, 23, 37, and 58% in humans, rabbits, rats, anddogs) reflecting differing degrees of first-pass metabolism. These data correlate well with hepatic extraction ratios, which are highest inrabbits and humans and lowest in dogs. Renal clearance is significantin all species and exceeds the glomerular filtration rate in rats, rabbits, and humans, but not in dogs. The compound is a weak base that shows widespread tissue distribution, including passage across the placental barrier and into milk, but low CNS penetration. Protein binding of sumatriptan is low in all species. Elimination half-lives of sumatriptan are approximately 1 hr in rats and rabbits, and approximately 2 hr in dogs and humans. In all species the majority of the absorbed dose is renally excreted, predominantly as the indole acetic acid metabolite and unchanged drug. Interesting species differences are evident inthe metabolism of sumatriptan. Thus, in humans, the indole acetic acid metabolite is excreted partly as a glucuronide, whereas in animals conjugation of this metabolite is not apparent. In addition, demethylation of the sulfonamide side chain of the drug is evident in rodent andlagomorph species only.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 14:24:34