RESUMO
Four derivatives of 4-isobutylphenyl-2-propionic acid (Ibuprofen), in which the drug was bound by ester linkages to poly(ethylene glycols) (PEG 2000-I), monomethoxy poly(ethylene glycols) (PEG 1900-I), poly(N-vinyl pyrrolidinone) (PVP-I) and poly(N-acryloyl morpholine) (PACM-I), all having approximatively the same number average molecular weight (Mn congruent equal to 2000), were prepared and tested for their pharmacokinetic properties after oral administration. It was found that the two end-hydroxylated amphiphilic oligomers of polyvinylic structure, PACM and PVP, whose physico-chemical properties are comparable to those of PEGs especially as regards solvent affinity, have in principle a similar potential as promoieties for preparing oligomeric prodrugs.
Assuntos
Materiais Biocompatíveis/química , Ibuprofeno/síntese química , Ibuprofeno/farmacocinética , Polietilenoglicóis/química , Pirrolidinonas/química , Resinas Acrílicas , Administração Oral , Animais , Sítios de Ligação , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Ésteres/síntese química , Ésteres/farmacocinética , Hidroxilação , Ibuprofeno/administração & dosagem , Ibuprofeno/sangue , Peso Molecular , Polímeros , Pró-Fármacos , Ratos , Ratos Sprague-Dawley , Solventes/metabolismo , Relação Estrutura-AtividadeRESUMO
Five prodrugs of S(+)-2-(6-methoxy-2-naphthyl)propionic acid (naproxen), in which the drug was bound by ester linkages to diethyleneglycol (I), triethyleneglycol (II), octanediol (III), butyl-triethyleneglycol (IV), and butyl-tetraethyleneglycol (V), respectively, were prepared and tested for their pharmacokinetic properties after oral administration. It was found that bioavailabilities decreased in the order, and in all cases were lower than that of the free drug.