Effect of malnutrition on the pharmacokinetics of cefuroxime axetil in young rats

Abstract

PURPOSE. To determine the pharmacokinetics of cefuroxime axetil in malnourished rats using a diet with a restriction in energy and nutrients (group M), a diet with a low quality protein (group K) and a good quality diet (group C) as a control. METHODS. The rats were fed with the corresponding diet for 21 days, after which a single oral dose of cefuroxime axetil (equivalent to a 2.2 mg dose of cefuroxime) was administered and plasma samples were taken at 0, 5, 10, 30, 45, 60, 90, 120, 180, 240, 300 and 360 minutes; samples were assayed using an HPLC assay. Biochemical parameters were measured and a microscopy study of the small intestine was carried out. After a 21 day period of recovery of the malnourished groups a second pharmacokinetic study was performed using the same sample times as those in the first study. RESULTS. In malnourished animals of group K the levels of plasma proteins were low and the concentrations of fat in the liver were high. The relative bioavailability of cefuroxime was 78.2% for group M and 64.4% for group K. Groups M and K presented lower values of area under the curve; this means that the amount of antibiotic absorbed was lower than that of group C. In the second pharmacokinetic study although the animals received a good quality diet, it was observed that the area under the curve of group K was lower; the relative bioavailability was 54.3%, while group M had pharmacokinetic values similar to those of the control group. CONCLUSIONS. The pharmacokinetics of cefuroxime was affected by malnutrition, suggesting that the absorption process via the transporter was modified in the malnourished groups, especially in the group fed with low quality protein.