Effect of food on the pharmacokinetics of oral cefuroxime axetil in dogs

Abstract

Cefuroxime axetil pharmacokinetic profile was investigated in 12 Beagle dogs after single intravenous and oral administration of tablets or suspension at a dose of 20mg/kg, under both fasting and fed conditions. A three-period, three-treatment crossover study (IV, PO under fasting and fed condition) was applied. Blood samples were withdrawn at predetermined times over a 12-hr period. Cefuroxime plasma concentrations were determined by HPLC. Data were analyzed by compartmental analysis. No statistically significant differences were observed between formulations and feeding conditions on PK parameters. Independently of the feeding condition, absorption of cefuroxime axetil after tablet administration was low and erratic. The drug has been quantified in plasma in 3 out of 6 and 5 out of 6 dogs in the fasted and fed groups. For this formulation, the bioavailability (F), peak plasma concentration (Cmax ), and area under the concentration-time curve (AUC) of cefuroxime axetil were significantly enhanced (p<.05) by the concomitant ingestion of food (32.97±13.47-14.08±7.79%, 6.30±2.62-2.74±0.66µg/ml, and 15.75±3.98-7.82±2.76µg.hr/ml for F, Cmax, and AUC in fed and fasted dogs, respectively), while for cefuroxime axetil suspension, feeding conditions affected only the rate of absorption, as reflected by the significantly shorter absorption half-life (T½(a) ) and time to peak concentration (Tmax ) (0.55±0.27-1.15±0.19hr and 1.21±0.22-1.70±0.30 for T½(a) and Tmax in fed and fasted dogs, respectively). For cefuroxime axetil tablets, T>MIC (≤1µg/ml) was <2hr in fasted and ≈4hr in fed animals, and for cefuroxime axetil suspension, T>MIC (≤1µg/ml) was ≈5hr and for T >MIC (≤4µg/ml) was ≈2.5hr for fasted and fed dogs, respectively. Cefuroxime axetil as a suspension formulation seems to be a better option than tablets. However, its short permanence in plasma could reduce its clinical usefulness in dogs.