Carbenicillin prodrugs: kinetics of intestinal absorption competing degradation of the alpha-esters of carbenicillin and prediction of prodrug absorbability from quantitative structure-absorption rate relationship.

The intestinal absorption of alpha-esters of carbenicillin disodium, carbenicillin phenyl sodium, and carbenicillin indanyl sodium was investigated using the in situ rat intestinal recirculating method. In the in situ intestinal lumen at pH 7, two prodrugs were rapidly converted to poorly absorbable carbenicillin, possibly by the action of intestinal nonspecific esterase in competition with the slow absorption of prodrugs. At pH 5, the reduced action of esterase and the increased absorption rate after 3 hr resulted in 50 and 60% absorption of carbenicillin phenyl sodium and carbenicillin indanyl sodium, respectively. The absorption rate constants determined for both prodrugs were in good agreement with the prediction from the quantitative structure-absorption rate relationship derived from the two-compartment aqueous diffusion model.