desacetylcefotaxime and Kidney-Diseases

It is generally assumed that the renal clearance of drugs in patients with renal impairment are affected to a similar extent regardless of the type of renal disease (intact nephron hypothesis). We have studied the effect of underlying renal disease on the pharmacokinetics of cefotaxime and desacetylcefotaxime in two groups of children (ages 7 to 16 y) with varying degrees of renal dysfunction. Patients in group 1 (n = 5) had intrinsic renal disease and those in group 2 (n = 5) had extrinsic renal disease, as identified by the primary renal lesion. After a single intravenous dose of cefotaxime timed blood and urine samples were collected for 24 h; cefotaxime and desacetylcefotaxime were measured by HPLC. There were no significant differences between the groups in age, body surface area, urine output, creatinine clearance, total body clearance, nonrenal clearance, renal clearance, and volume of distribution at steady state of cefotaxime, and renal clearance of desacetylcefotaxime. However, the renal clearance: creatinine clearance (CLR:CLCR) ratios for both cefotaxime [1.34 in group 1 vs. 0.51 in group 2] and desacetylcefotaxime [1.58 in group 1 vs. 0.75 in group 2] were statistically significant between the two groups. Group 1 patients had an average CLR:CLCR ratio greater than 1 for both the parent compound and the metabolite, suggesting that net tubular secretion was still intact, despite a diminished glomerular filtration rate (CLCR = 24 ml.min-1.73 m-2).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Cefotaxime; Child; Creatinine; Humans; Kidney Diseases; Pharmaceutical Preparations; Regression Analysis; Urodynamics

We studied cefotaxime (CTX) and desacetylcefotaxime (dCTX) pharmacokinetics in 19 children (ages, 7 to 16 years) with various degrees of renal function. The patients were stratified into three groups according to 24-h urinary creatinine clearance (CLCR) values: group I, CLCR greater than 80 ml/min/1.73 m2 (n = 7); group II, CLCR from 30 to 80 ml/min/1.73 m2 (n = 6); and group III, CLCR less than 30 ml/min/1.73 m2 (n = 6). A single 50-mg/kg dose of CTX was given intravenously to each patient after which blood and urine samples were collected and analyzed for CTX and dCTX by high-performance liquid chromatography. Safety was assessed by pre- and poststudy blood chemistries and urinalysis. The mean values for total body clearance of CTX for groups I, II, and III were 158.1 +/- 38.8, 118.3 +/- 50.8, and 84.8 +/- 11.7 ml/min/1.73 m2, respectively (P less than 0.01). Renal clearance also decreased across groups, I, II, and III, with values of 77.5 +/- 20.2, 41.3 +/- 18.5, and 11.4 +/- 7.7 ml/min/1.73 m2 respectively (P less than 0.0001). Both the CTX fraction nonrenally cleared and elimination half-life increased with decreasing renal function. The CTX volume of distribution at steady state was not affected by renal disease. The renal clearance values of dCTX were 146.4 +/- 71.4, 64.5 +/- 32.1, and 14.4 +/- 8.7 ml/min/1.73 m2 for groups I, II, and III, respectively (P less than 0.0004). Elimination half-life values were 2.04 +/- 0.39, 3.87 +/- 1.93, and 6.19 +/- 3.22 h for the respective groups (P less than 0.006). Both the maximum concentration of dCTX in plasma and time to reach the maximum concentration of dCTX in plasma were increased with decreased CLCR. The results of this study indicate that dosage adjustment may be necessary for CTX in children with renal dysfunction. On the basis of the pharmacokinetics and antimicrobial activities of the parent drug and its metabolite, dosage reductions of 25 to 50% in children with moderate renal impairment (CLCR from 30 to 80 ml/min/1.73 m2) and 50 to 75% in children with severe renal impairment (CLCR < 30 ml/min/1.73 m2) are recommended.

Topics: Adolescent; Cefotaxime; Child; Half-Life; Humans; Infusions, Intravenous; Kidney Diseases

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

Plasma concentrations of cefotaxime and desacetyl cefotaxime were determined by HPLC in geriatric patients with multiple diseases. Comparison with a younger control group of healthy volunteers showed a prolongation of half-life of CTX and dCTX in the older patients. A significant correlation between pharmacokinetic parameters of dCTX and other clinical and chemical parameters was found. Half-life of dCTX was positively correlated with age of the geriatric patients (P less than 0.05). There was also a significant relationship between CHE in serum and plasma peak concentrations of dCTX. Time until reaching plasma peak concentrations correlated closely with total bilirubin (P less than 0.01), CHE (P less than 0.001), cholesterol (P less than 0.01), and urea (P less than 0.01). Accumulation of the pharmacologically active metabolite dCTX could not be excluded in one patient with kidney disease. In accordance with other investigators it is recommended to reduce the dose of cefotaxime in geriatric patients with kidney diseases.

Topics: Aged; Arteriosclerosis; Cefotaxime; Diabetes Complications; Diabetes Mellitus; Diabetic Angiopathies; Female; Half-Life; Heart Failure; Humans; Hypertension; Kidney Diseases; Kinetics; Male; Pneumonia; Urinary Tract Infections

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