Pharmacokinetics and pharmacodynamics of tepoxalin after single oral dose administration to healthy volunteers.
J Clin Pharmacol
; 36(5): 462-8, 1996 May.
Article
em En
| MEDLINE
| ID: mdl-8739025
ABSTRACT
This study was conducted to examine the pharmacokinetics and pharmacodynamics of tepoxalin in healthy volunteers, an antiinflammatory compound that inhibits cyclooxygenase and lipoxygenase. Tepoxalin was absorbed after oral administration of single doses from 35 to 300 mg, after which it was rapidly converted to an acidic metabolite, RWJ 20142, which inhibits cyclooxygenase but not lipoxygenase. The areas under the concentration-time curve (AUC) of tepoxalin and RWJ 20142 in plasma increased in a dose-dependent fashion. Administration of the lowest dose of tepoxalin completely inhibited whole blood cyclooxygenase for the entire period of observation. This inhibition correlated closely with that of secretion and aggregation induced by collagen of platelets obtained from these subjects. Similarly, administration of tepoxalin was associated with significant inhibition of lipoxygenase in whole blood. Lipoxygenase was inhibited a maximum of 60% in a time-dependent fashion, and the duration of inhibition was dose-dependent. These studies demonstrate that tepoxalin inhibits whole blood cyclooxygenase, lipoxygenase, and platelet function after oral administration in humans.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Anti-Inflamatórios não Esteroides
/
Inibidores de Lipoxigenase
/
Inibidores de Ciclo-Oxigenase
Tipo de estudo:
Clinical_trials
Limite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
J Clin Pharmacol
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos