Cefadroxil kinetics in patients with renal insufficiency

Kinetic parameters and bioavailability of cefadroxil were studied in 20 subjects with differing renal function as measured by endogenous creatinine clearance (CCr). Two subjects were on hemodialysis. After an overnight fast, each subject ingested two 500-mg capsules of cefadroxil. The peak serum concentration was variable (12 to 57 mg/l) and correlated inversely with the CCr. All but one patient had maximum absorption within 4 hr of ingestion and in most patients the peak was reached within the 2-hr sample. Urinary recovery within 48 hr was 45% to 106% when CCr > 8 ml/min. Even in patients with the most severe renal failure (CCr < 10 ml/min), urine concentrations of cefadroxil were adequate to treat susceptible bacteria. The rate of oral absorption, ka, was not affected by the state of renal function and was 0.76 ± 0.50 hr−1. The apparent distribution volume Vd ext was 0.28 ± 0.09 l/kg. The plasma elimination rate was dependent on CCr with a small fraction of drug being removed by nonrenal routes. Except in advanced renal failure, tubular secretion was present since renal clearance of cefadroxil exceeded CCr. The data suggest that little drug accumulation will occur with the usual 8- to 12-hr dosing schedule except when the CCr is less than 25 ml/min.