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Titolo:
Pharmacokinetics and metabolism of a sulphamide NK2 antagonist in rat, dogand human
Autore:
Beaumont, K; Harper, A; Smith, DA; Abel, S;
Indirizzi:
Pfizer Ltd, Cent Res, Dept Drug Metab, Sandwich CT13 9NJ, Kent, England Pfizer Ltd Sandwich Kent England CT13 9NJ andwich CT13 9NJ, Kent, England Pfizer Ltd, Cent Res, Early Clin Res Grp, Sandwich CT13 9NJ, Kent, EnglandPfizer Ltd Sandwich Kent England CT13 9NJ andwich CT13 9NJ, Kent, England
Titolo Testata:
XENOBIOTICA
fascicolo: 6, volume: 30, anno: 2000,
pagine: 627 - 642
SICI:
0049-8254(200006)30:6<627:PAMOAS>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
P-GLYCOPROTEIN; DRUG-DELIVERY; BLOOD-CELLS; BIOAVAILABILITY; ABSORPTION; PEPTIDES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
16
Recensione:
Indirizzi per estratti:
Indirizzo: Beaumont, K Pfizer Ltd, Cent Res, Dept Drug Metab, Sandwich CT13 9NJ, Kent, England Pfizer Ltd Sandwich Kent England CT13 9NJ 9NJ, Kent, England
Citazione:
K. Beaumont et al., "Pharmacokinetics and metabolism of a sulphamide NK2 antagonist in rat, dogand human", XENOBIOTICA, 30(6), 2000, pp. 627-642

Abstract

1. UK-224,671 is a sulphamide-containing NK2 antagonist with moderate lipophilicity and basicity.2. The physicochemical properties of UK-224,671 are reflected in its pharmacokinetics following intravenous (i.v.) administration. The compound partitioned extensively into red blood cells in all species examined and the blood clearance was moderate to low with respect to liver blood flow and distribution into tissues was extensive.3. UK-224,671 exhibited species differences in oral bioavailability. In dog, the compound exhibited moderate bioavailability (55%), whereas in rat and man oral bioavailability was <10%.4. In rat and dog, the major excreted form after i.v. administration was unchanged UK-224,671 in both urine and faeces. In addition, of three metabolites observed, the most abundant was the N-descyclopropylmethyl (UK-280,045).5. The profile of radioactivity in rat following oral administration of [C-14]-UK-224,671 was not consistent with a 10% absorbed compound with 40% ofthe dose present as metabolites. This suggests that the low bioavailability of UK-224,671 in rat is due to a combination of moderate intestinal permeability and extensive first-pass metabolism by the gut and does not result from poor gastrointestinal absorption per se.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 04:05:27