PHARMACOKINETICS OF CEFUROXIME AXETIL IN PATIENTS WITH NORMAL AND IMPAIRED RENAL-FUNCTION

The pharmacokinetics of cefuroxime axetil were studied by a model-independent method after a single oral dose corresponding to 500 mg of cefuroxime in 28 subjects grouped according to renal functions. Creatinine clearance (Clcr) was > 85, 50 to 84, 15 to 49, and < 15 mL/min in groups 1, 2, 3, and 4 respectively. The Varea/F (distribution volume/bioavailability) was independent of renal function, the average being 0·82 ± 0·27 L/kg. Both Cls/F (systemic clearance/bioavailability) and Clr (renal clearance) decreased linearly with the decrease in Clcr,. The T2-Jan (serum half-life) was 1·4± 0·33h, 2·4±0·65 h, 4·6±2·32 h, and 16·8± 10·2h in groups 1, 2, 3, and 4 respectively. A significant correlation existed between kel (elimination rate constant) and Clcr (r = 0·88, P < 0·01). kel of cefuroxime can be predicted by: kel (h-1)=0·0046 × Clcr plus; 0·0108. Based on these data, modification of dosing schedule is not deemed necessary when Clcr is above 50 mL/min/1·73 m2 while the standard individual dose should be given every 12 h when Clcr, is 49-30 mL/min/1·73 m2 every 24 h when it is 29-10 mL/min/1·73 m2 and every 48 h when it is below 10 mL/min/1·73 m2. © 1993 The British Society for Antimicrobial Chemotherapy.