FUROSEMIDE PRODRUGS - SYNTHESIS, ENZYMATIC-HYDROLYSIS AND SOLUBILITY OF VARIOUS FUROSEMIDE ESTERS

Various esters of furosemide were prepared and assessed as potential prodrugs with the aim of enhancing the peroral absorption characteristics of the parent drug. The esters studied included a neutral alkyl ester, alkyl esters containing an amino group, glycolamide esters and an O-acyloxymethyl ester. The esters showed widely different susceptibilities to undergo enzymatic hydrolysis in human plasma and rat liver homogenate, the propionyloxymethyl ester being the most reactive compound. The amino-containing esters were most soluble in water whereas all the esters were more lipophilic than furosemide as expressed by octanol-pH 7.4 buffer partition coefficients. © 1990.