desacetylcefotaxime and Liver-Diseases

The dispositions of cefotaxime and its metabolite desacetylcefotaxime were investigated in patients with different forms of chronic parenchymal liver disease (CPLD). A total of 31 subjects (27 patients and 4 controls) received a single 2-g dose of cefotaxime by infusion, and serial blood samples were drawn. The area under the concentration-time curve ranged from 176 to 241 micrograms.h/ml, the apparent half-life ranged from 1.49 to 2.42 h, and clearance ranged from 2.06 to 3.10 ml/min/kg in patients with four different forms of CPLD. The area under the concentration-time curve and the apparent half-life of desacetylcefotaxime ranged from 72 to 128 micrograms.h/ml and 7.1 to 13.4 h, respectively. Pharmacokinetic parameters were significantly different in patients with CPLD compared with those in control subjects and were related to clinical indices of hepatic impairment. Modest accumulation of cefotaxime in patients with severe hepatic impairment is unlikely to produce toxicity because of its high therapeutic index, and dosing modifications may not be required.

Topics: Adult; Cefotaxime; Chromatography, High Pressure Liquid; Chronic Disease; Half-Life; Humans; Liver Diseases; Middle Aged

Serum levels of cefotaxime and desacetyl-cefotaxime were studied in 18 patients with hepatic cirrhosis after an intravenous bolus injection of 2 g of cefotaxime. Blood levels were independent of the degree of hepatic dysfunction and did not differ from those reported in normal individuals.

Topics: Adult; Aged; Cefotaxime; Female; Humans; Liver Cirrhosis; Liver Diseases; Male; Middle Aged

We developed a protocol to study interference by cefotaxime and one of its major metabolites with 24 common chemical tests. Serum pools simulating specimens from healthy adults of both sexes, pregnant women, patients with liver disease, cardiac disease, or renal disease, and patients receiving gentamicin and tobramycin were supplemented with high and low concentrations of cefotaxime and desacetylcefotaxime. Using a discrete analyzer (the American Monitor Parallel), we tested 12 replicate samples from each condition for 24 analytes. Although statistically significant changes were found in many tests, 85% of the differences were less than 15% of the control value and more than half were less than 5%. The apparent concentration of creatinine was not significantly changed. Test results for phosphorus were increased in patients who were receiving gentamicin and tobramycin. No other changes were considered clinically significant.

Topics: Blood Chemical Analysis; Cefotaxime; False Positive Reactions; Female; Gentamicins; Heart Diseases; Humans; Kidney Diseases; Liver Diseases; Male; Pregnancy; Probability; Tobramycin

The pharmacology of cefotaxime and the metabolite desacetyl cefotaxime was studied in 40 patients with various degrees of renal and hepatic failure who received 0.5 or 1 g of cefotaxime intravenously. Patients with severe renal impairment (creatinine clearance, 3 to 10 ml/min) had a cefotaxime serum half-life of 2.6 h and desacetyl cefotaxime serum half-life of 10.0 h. The equivalent figures were 1.0 and 1.5 h, respectively, in subjects with normal renal function. The presence of an acute coexisting illness together with severe renal impairment was associated with a further prolongation of the serum half-lives. Hepatic dysfunction was accompanied by a reduction in desacetyl metabolite formation. A reduction of cefotaxime dosing to 0.5 g twice a day would appear prudent when the creatinine clearance is 5 ml/min or less to avoid accumulation of the parent compound and the metabolite.

Topics: Cefotaxime; Cephalosporins; Female; Half-Life; Humans; Kidney Diseases; Kidney Failure, Chronic; Kinetics; Liver Diseases; Male; Middle Aged