Pharmacokinetics of Cefotaxime and Desacetyl-Cefotaxime in Cirrhosis of the Liver

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Abstract
In 9 patients with advanced hepatic cirrhosis and a normal serum creatinine concentration, the pharmacokinetics of cefotaxime (CTX) and its desacetyl metabolite (DACM) were examined in serum and urine after intravenous administration of 2.0 g CTX. The peak serum levels were 130.3 ± 33.9 and 8.5 ± 4.6 mg/l for CTX and DACM, respectively. T50%β was calculated to be 138.1 min (69.3–245.8 min) for CTX. The approximation of the terminal half-life of DACM revealed a prolongation which exceeded 10 h. Accordingly, the AUC amounted to 255.3 ± 92.0 and 151.9 h x mg/l, respectively. Within 24 h, 62.9% was eliminated in urine as CTX and 19.4% as DACM. The total clearance of CTX was reduced to 164.3 ml/min (58.3–296.6 ml/min), but the renal clearance was only moderately decreased to 90.0 ml/min (24.1–169.3 ml/min). These altered kinetics can be explained by altered metabolic function of the liver as well as by cirrhosis-linked alterations of renal elimination mechanisms.

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