Pharmacokinetic assessment of cefpodoxime proxetil in diabetic rats.

Abstract

In diabetes, multi-organ level dysfunction arising from metabolic complications is reported to influence the pharmacokinetics (PK) profile of many drugs. Hence, the present study was planned in rats to evaluate the effect of diabetes on the PK profile of cefpodoxime, a widely prescribed oral antibiotic. PK profile of cefpodoxime was assessed after oral administration of cefpodoxime proxetil (10 and 20mg/kg) and intravenous (i.v) administration of cefpodoxime sodium (10mg/kg) in normal and streptozotocin induced diabetic rats. To evaluate the impact of diabetes on oral absorption and serum protein binding, in situ intestinal permeability and in vitro serum protein binding studies were performed for cefpodoxime using Single Pass Intestinal Perfusion model (SPIP) and ultracentrifugation technique, respectively. In diabetic rats, there was significant (p < 0.01) decrease in maximum concentration (Cmax) and area under the curve (AUC) of cefpodoxime by both oral and intravenous route, which was attributed to augmented clearance of cefpodoxime. There was no change in the time to achieve Cmax (Tmax) suggesting no alteration in oral absorption which was further confirmed through unaltered intestinal permeability in diabetic rats. The protein binding in diabetic rats also remained unchanged, indicating no influence of protein binding on elevated clearance. The plasma exposure of cefpodoxime, a renally eliminated drug was significantly lowered in diabetic rats due to enhanced glomerular filtration. However, this observation needs to be confirmed through well controlled clinical trials.