Design, synthesis, bioconversion, and pharmacokinetics evaluation of new ester prodrugs of olmesartan.
Eur J Med Chem
; 46(9): 3564-9, 2011 Sep.
Article
em En
| MEDLINE
| ID: mdl-21641692
ABSTRACT
Synthesis of new ester prodrugs of olmesartan is described. Their in vitro stabilities in simulated gastric juice, rat plasma, and rat liver microsomes were tested. And the pharmacokinetic parameters for olmesartan after their oral administration were also estimated and compared with those in case of olmesartan medoxomil. Compounds 13 and 14 demonstrated high stability in simulated gastric juice and were rapidly metabolized to olmesartan in rat liver microsomes and rat plasma in vitro. In addition, C(max) and AUC(last) parameters were significantly increased in case of compounds 13 and 14 compared with olmesartan medoxomil. These results indicate that compounds 13 and 14 with cyclohexylcarboxyethyl and adamantylcarboxymethyl promoieties, respectively, are promising prodrugs of olmesartan with markedly increased oral bioavailability.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tetrazóis
/
Pró-Fármacos
/
Desenho de Fármacos
/
Bloqueadores do Receptor Tipo 1 de Angiotensina II
/
Imidazóis
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2011
Tipo de documento:
Article