cefuroxime-axetil and Renal-Insufficiency

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 V(area)/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 T1/2 (serum half-life) was 1.4 +/- 0.33 h, 2.4 +/- 0.65 h, 4.6 +/- 2.32 h, and 16.8 +/- 10.2 h 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 x Clcr + 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.

Topics: Adult; Aged; Cefuroxime; Female; Humans; Male; Metabolic Clearance Rate; Middle Aged; Prodrugs; Renal Insufficiency