Improvement of cefpodoxime proxetil oral absorption in rats by an oil-in-water submicron emulsion.

摘要

Absolute bioavailability of cefpodoxime proxetil is both limited by its low solubility in aqueous solution and its intraluminal hydrolysis. The oil-in-water submicron emulsion was proven to be effective in protecting the prodrug from the enzymatic attack in rabbit intestinal washings. The aim of the study was to perform a pharmacokinetic study in conscious rats to confirm o/w submicron superiority in comparison to other oral formulations (hydro-alcoholic solution, suspension and coarse emulsion). The pharmacokinetic study was performed in conscious rats implanted with permanent aortic catheters. A parenteral solution of cefpodoxime was injected via this catheter, and oral formulations were administered orally. The cefpodoxime plasma level was performed by a HPLC validated method. The pharmacokinetic parameters, t1/2, Cmax, tmax, AUC and absolute bioavailability (F) were determined with a non-compartmental analysis. The results show a significant increase of F for submicron emulsion (97.4%) between the other oral formulations. No significant difference of F was found between the other oral formulations, even with the coarse o/w emulsion. The o/w submicron emulsion made the enhancement of the absolute bioavailability of cefpodoxime proxetil possible. This benefit could be explained by the low droplet size of the submicron emulsion which improve the absorption process of the prodrug.