cefmenoxime and Kidney-Diseases

The pharmacokinetics of cefmenoxime were studied after a single intravenous 1.0-g dose to 24 subjects grouped according to their renal functions. Creatinine clearance was above 85, 50 to 85, 10 to 50, and below 10 ml/min per 1.73 m2 in groups 1, 2, 3, and 4, respectively. Cefmenoxime obeyed two-compartment-model kinetics in all four groups. The volume of distribution based on the area under the serum concentration-time curve was renal function independent, the average value being 0.270 +/- 0.075 liters/kg. The elimination-phase half-life (t1/2 beta) was 0.82 +/- 0.30 h in group 1, 1.38 +/- 0.36 h in group 2, 3.32 +/- 1.82 h in group 3, and 7.60 +/- 1.28 h in group 4. Cumulative 24-h urinary excretion accounted for 65.5 +/- 7.6% of the dose in group 1 and for 7.50 +/- 3.72% in group 4. Recommendations for dosage adjustment in patients with renal insufficiency are proposed based on the data obtained in this study. The effect of hemodialysis on cefmenoxime pharmacokinetics was studied in six patients in group 4; hemodialysis shortened the average t1/2 beta from 7.60 +/- 1.28 to 4.19 +/- 1.66 h. It was estimated that in a hypothetical anephric subject with a body weight of 60 kg, 5-h hemodialysis would remove 28.2% of the drug present in the body at the start of hemodialysis.

Topics: Adult; Cefmenoxime; Cefotaxime; Female; Humans; Kidney; Kidney Diseases; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Renal Dialysis

The pharmacokinetics of cefmenoxime were determined after a 30-min intravenous infusion of 15 mg/kg of total body weight to 33 adult subjects with normal renal function (CLCR, greater than 80 ml/min per 1.73 m2, group I), mild renal insufficiency (CLCR, 40 to 79 ml/min per 1.73 m2, group II), moderate renal insufficiency (CLCR, 10 to 39 ml/min per 1.73 m2, group III), or severe renal impairment, (CLCR, less than 10 ml/min per 1.73 m2, group IV) or to patients between hemodialysis (CLCR, less than 10 ml/min per 1.73 m2, group V). Concentrations of cefmenoxime in serum and urine were determined by high-pressure liquid chromatography, and serum concentrations were fit to a two-compartment model. There was no significant relationship between creatinine clearance and either peak serum concentrations or volume of distribution at steady state. Patients in group I excreted 81% of the dose into the urine within 24 h; recovery decreased with worsening renal function. The mean terminal half-lives in groups I to V were 1.06, 1.50, 3.55, 4.60, and 11.4 h, respectively. There were good linear relationships between creatinine clearance, and the elimination rate and total body clearance of cefmenoxime. Dosage recommendations for subjects with renal insufficiency are proposed.

Topics: Cefmenoxime; Cefotaxime; Creatinine; Female; Half-Life; Humans; Kidney Diseases; Kinetics; Male; Metabolic Clearance Rate

The pharmacokinetics of cefmenoxime were characterized in five healthy volunteers and in 15 subjects with various degrees of renal insufficiency after a single 10-mg/kg, 5-min intravenous infusion. Five of these subjects were studied both on hemodialysis and during an interdialytic period. Plasma, urine and dialysate were assayed for cefmenoxime by a specific high-pressure liquid chromatographic assay. Peak plasma concentrations of cefmenoxime were ca. 94 micrograms/ml after completion of the infusion. The mean plasma and renal clearances in the healthy volunteers were 281 +/- 66 and 228 +/- 52 ml/min, respectively. Plasma clearance declined in patients with renal insufficiency and correlated significantly with creatine clearance. The mean apparent volume of distribution at steady state in the healthy volunteers was 0.23 liters/kg and was not found to be significantly different in subjects with renal insufficiency. The mean cumulative 24-h urinary recovery of cefmenoxime in healthy volunteers was 81% of the administered dose and decreased with reduced renal function. Cefmenoxine dosage should be reduced in proportion to the decline in creatinine clearance. A simple nomogram for dose selection is provided.

Topics: Adult; Aged; Cefmenoxime; Cefotaxime; Chromatography, High Pressure Liquid; Creatinine; Female; Humans; Kidney Diseases; Kidney Function Tests; Kinetics; Male; Middle Aged; Renal Dialysis

7 beta-[2-(2-Aminothiazol-4-yl)-(Z)-2-methoxy-iminoacetamido]-3-[(1- methyl-1H-tetrazol-5-yl)thiomethyl]-ceph-3-em-4-carboxylic acid hemihydrochloride (Cefmenoxime), a new cephalosporin with a broad spectrum of activity against gram-positive and gram-negative bacteria, was investigated pharmacokinetically. 10 healthy volunteers and 20 patients with renal disease each received 2 g of the substance i.v. The plasma levels were monitored for 6 h in healthy volunteers and for 24 h in the patients with renal disease. The analysis of the data showed that the majority of the curves could be properly evaluated only with the aid of a two-compartment model. Therefore a simple half-life cannot be given. Cefmenoxime is eliminated more rapidly than cefoperazone, but more slowly than cefotaxime. The area under the serum level curves (AUC) increases when renal function is impaired. There is a mathematical correlation between the AUC and the renal function parameters, plasma creatinine and glomerular filtration rate. This gives the dose reduction factors, allowing the calculation of the doses with the same AUC on restricted renal function as that observed in healthy persons after normal doses. Dosage recommendations are given in the form of tables regarding the questions 1. to what extent the dose may be reduced in impaired renal function without lowering the AUC and 2. what is the highest safe dose.

Topics: Cefmenoxime; Cefotaxime; Creatinine; Female; Glomerular Filtration Rate; Half-Life; Humans; Injections, Intravenous; Kidney Diseases; Kinetics; Male