Bioavailability of cefuroxime axetil: comparison of standard and abbreviated methods

A randomized cross-over study comparing serum and urinary concentrations of cefuroxime after a 750 mg intravenous dose of cefuroxime and a 500 mg oral dose of cefuroxime axetil was conducted to evaluate the bioavailability of the current marketed formulation of cefuroxime axetil. The absolute bioavailability was compared with various abbreviated methods of assessing bioavailability. The peak concentrations (Cmax) and times to peak (Tmax) varied considerably (range 4.7-12.0 mg/l and 1.5-4 h respectively). The absolute bioavailability was 67.9%. The urine recovery after oral dosage and urine bioavailability were 38.6% and 50.3% respectively. The mean AUC0-6 h after the oral dosage was 27.7 mg/l.h. Both urine recovery and urine bioavailability were poor indicators of bioavailability (r = 0.54, r = 0.33 respectively). Although AUC0-6 h after the oral dose was positively correlated with absolute bioavailability, the coefficient of determination (r2) indicated that only 56% of the variation in absolute bioavailability was explained by AUC0-6 h. This study demonstrated that the current formulation of cefuroxime axetil is reliably absorbed although there is considerable variation in Cmax and Tmax. Because of this variation and because the abbreviated methods were unsatisfactory, we recommend that bioavailability of cefuroxime axetil in patients should be measured by formal intravenous/oral cross-over serum concentration studies.