cefamandole and Kidney-Failure--Chronic

The treatment of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) usually includes the repeated administration of intraperitoneal (ip) antibiotics. The initial segment of this study (15 noninfected CAPD patients) examined the ip administration of four structurally different agents that represent the common types of antibiotics prescribed for peritonitis: an aminoglycoside (tobramycin), a glycopeptide (vancomycin), a beta-lactam (cefamandole), and an oxa-beta-lactam (moxalactam). Subsequently, 16 CAPD patients with peritonitis received either vancomycin (30 mg/kg) or cefamandole (1 g) in two liters of dialysate over a six-hour dwell period. Vancomycin and cefamandole were absorbed more rapidly in patients with peritonitis as indicated by a more rapid decline in dialysate concentrations, and higher serum concentrations that occurred earlier than in the noninfected patients. Although a higher percentage of the ip dose of vancomycin and cefamandole was absorbed during peritonitis, peak serum concentrations at the end of the drug administration dwell period were not significantly different. Numerous factors influence the absorption of ip antibiotics, including the dialysate drug concentration, the dwell period, protein binding, distribution volume, and presence or absence of peritonitis.

Topics: Absorption; Anti-Bacterial Agents; Cefamandole; Humans; Infusions, Parenteral; Kidney Failure, Chronic; Moxalactam; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Radioimmunoassay; Tobramycin; Vancomycin

The pharmacokinetic characteristics of cefonicid, a highly protein-bound expanded-spectrum cephalosporin, were examined in six noninfected, clinically stable patients undergoing continuous ambulatory peritoneal dialysis. After a 1.0-g intravenous dose of cefonicid, the mean concentrations in serum were 105 +/- 25 and 35.6 +/- 14.4 micrograms/ml at 3 and 72 h, respectively. Despite a prolonged half-life in serum of 49.7 +/- 18 h, the penetration into peritoneal fluid was low. The average concentration in dialysate over the 72-h study period was 2.7 micrograms/ml. The serum clearance was 2.6 +/- 1.0 ml/min, and the distribution volume was 0.14 +/- 0.02 liter/kg. Dosage recommendations and clinical considerations for cefonicid use in continuous ambulatory peritoneal dialysis patients are discussed.

Topics: Cefamandole; Cefonicid; Humans; Kidney Failure, Chronic; Kinetics; Peritoneal Cavity; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis

The 1-methyl-1 H-tetrazole-5-thiol (MTT) side chain present on several new cephalosporins may be an important factor in coagulopathy observed during therapy with these antibiotics. To determine the plasma kinetics and protein binding of the side chain and to test the hypothesis that renal failure alters these parameters, we gave six normal volunteers and six anuric patients a single iv dose of 15 mg of cefamandole/kg. Plasma concentrations of cefamandole and free MTT were measured by high-performance liquid chromatography 14 times during the 48-hr period after the dose was given. A compartment-independent pharmacokinetic analysis showed that MTT was rapidly removed from the plasma of normal subjects, but that peak concentrations of MTT were nearly three times greater and persisted for 48 hr in patients with renal failure. Further, renal failure caused a significant MTT protein-binding defect. If a relation exists between hypoprothrombinemia and plasma concentrations of MTT side chain, patients with reduced renal function may be at increased risk for this adverse effect.

Topics: Adult; Azoles; Blood Proteins; Cefamandole; Humans; Kidney Failure, Chronic; Male; Metabolic Clearance Rate; Middle Aged; Protein Binding; Structure-Activity Relationship; Tetrazoles

Cefamandole disposition kinetics were examined in six male subjects with renal impairment who were undergoing continuous ambulatory peritoneal dialysis. Creatinine clearance values ranged from less than 1 to 11 ml/min. Cefamandole was given as a 1-g intravenous dose infused over 30 min. Cefamandole concentrations were determined in serum, urine, and dialysis fluid by a high-performance liquid chromatographic method. The following average parameter values were obtained (range): half-life, 6.1 h (4.6 to 9.7); systemic clearance, 21.9 ml/min (8.4 to 35.5); renal clearance, 11.5 ml/min (0.03 to 22.3); dialysis clearance, 0.92 ml/min (0.7 to 1.3); nonrenal clearance, 12.2 ml/min (2.9 to 27.0); volume of distribution, 0.18 liter/kg (0.09 to 0.25); steady-state volume of distribution, 0.17 liter/kg (0.09 to 0.24). Approximately 5% of the dose was dialyzed (range, 2.8 to 8.3), indicating that there is no need to supplement a dosing regimen of cefamandole due to loss by dialysis. There was a positive correlation between creatinine clearance and the terminal elimination rate constant of cefamandole (r2 = 0.41) and cefamandole renal clearance (r2 = 0.83).

Topics: Cefamandole; Humans; Kidney; Kidney Failure, Chronic; Kinetics; Male; Metabolic Clearance Rate; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory

A pharmacokinetic model and distributional clearance terms to describe bidirectional peritoneal transfer were used to examine cefamandole pharmacokinetics in five uninfected patients with end-stage renal disease who were receiving continuous ambulatory peritoneal dialysis. Each patient received intravenous and intraperitoneal 1 gm doses of drug, and serum and dialysate samples were collected over three dialysis dwell periods. The mean systemic availability of cefamandole after intraperitoneal dosing was 0.71 +/- 0.1. No significant differences in the serum-to-peritoneal fluid and peritoneal fluid-to-serum distributional clearances were observed. The time dependence of peritoneal dialysis clearance was examined. The amount of drug found in the dialysate divided by the corresponding serum AUC was empirically found to estimate the time-averaged peritoneal dialysis clearance. A mass balance-area method to calculate distributional clearance was developed that obviates more complicated computer fitting of the data. We present a comprehensive modeling approach that should be useful in the examination of the kinetics of drugs during continuous ambulatory peritoneal dialysis.

Topics: Adult; Cefamandole; Female; Humans; Injections, Intraperitoneal; Injections, Intravenous; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Models, Biological; Peritoneal Dialysis, Continuous Ambulatory

Ceforanide (500 mg) was infused intravenously over 30 min into six normal subjects, 10 nondialysis patients with renal insufficiency, and six hemodialysis patients. Dialysis patients received two ceforanide infusions, one immediately before dialysis and another during an interdialysis period. Sequential plasma samples over 24 to 72 hr were assayed for ceforanide. Peak ceforanide levels (mean = 69 +/- 12 micrograms/ml) and volumes of distribution did not vary with creatinine clearance (Clcr, ml/min/1.73 m2) and both plasma clearance and renal clearance decreased linearly as Clcr decreased. Mean nonrenal clearance (4.6 +/- 1.8 ml/min/1.73 m2) did not vary with Clcr. Mean half-life was 3 hr in the normal subjects, increasing to approximately 25 hr in patients with severe renal insufficiency. Hemodialysis resulted in a removal of approximately 21% of the dose of ceforanide. Dosing recommendations for patients with renal insufficiency are provided.

Topics: Adult; Aged; Cefamandole; Cephalosporins; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged

The pharmacokinetics of ceforanide were evaluated in 11 patients with end stage renal disease (creatinine clearance less than 5 ml/min). A single intravenous dose of 750 mg/m2 produced peak plasma concentrations of 123 +/- 29 microgram/ml. The plasma half-life (T 1/2) of the drug was 19.1 +/- 2.5 h. A 5.5 h hemodialysis session removed 53% of the drug and reduced the T 1/2 to 5 +/- 0.7 h. Plasma concentrations greater than 10 microgram/m2 were maintained without adverse effects with a 1.5-g/m2 dose administered three times a week for 2 weeks.

Topics: Adult; Aged; Cefamandole; Cephalosporins; Female; Half-Life; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Renal Dialysis

The pharmacokinetics of Cefamandole was studied in 17 patients with terminal renal impairment, 10 of which were undergoing sessions of hemodialysis while 7 were in the period between dialysis sessions. An open two-compartment kinetic model was used to describe the bi-phasic decrease of the plasma concentrations of Cefamandole thus establishing the amounts of the antibiotic in the peripheral and central compartments together with the amount eliminated. All patients received an i.v. bolus injections of 15 mg/kg body weight. During the hemodialysis sessions, the pharmacokinetic parameters of Cefamandole were the following: alpha = 5.006 hr-1 beta = 0.182 hr-1 K12 = 2.598 hr-1 K21 = 2.147 hr-1 K13 = 0.441 hr-1 Vc = 5.700 l Vp = 6.190 l Vdss = 11.94 l It may be seen that there is a decrease in the overall elimination constant compared with that obtained during the periods between the dialysis sessions. A dosage regimen of multiple doses is established as a function of the pharmacokinetic parameters of the antibiotic for patients with terminal renal impairment undergoing periodic sessions of hemodialysis.

Topics: Adolescent; Adult; Aged; Cefamandole; Cephalosporins; Female; Half-Life; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Renal Dialysis; Time Factors

The hydrolysis of cefamandole nafate was examined in vivo in five dialysis patients and five subjects with normal renal function. The plasma half-life of cefamandole was prolonged in the patients with renal failure compared with normal subjects (18.3 +/- 4.5 [standard deviation] versus 10.35 +/- 1.4 min, P less than 0.01). The pharmacokinetics of cefamandole nafate best fit two-compartment, open-model kinetics. We conclude that patients with severe renal failure are capable of hydrolyzing cefamandole nafate to cefamandole and formate at a rate sufficiently rapid so as not to allow an accumulation of cefamandole nafate. The difference in half-life may be related to urinary excretion of cefamandole nafate in normal individuals.

Topics: Adult; Aged; Cefamandole; Cephalosporins; Half-Life; Humans; Hydrolysis; Kidney Failure, Chronic; Kinetics; Middle Aged; Renal Dialysis; Time Factors

1.0 g cefamandol was injected in 25 patients with various degrees of renal function. Half-life and distribution volume of this antibiotic and the glomerular filtration rate (GFR) were then measured. The distribution volume was 18.5 +/- 3.5% of body weight, similar to the extracellular space. Half-life and GFR were related in a way which could be expressed in the formula: half-life = 400 sqaure root GFR. Levels of blood concentration of cefamandol could be estimated from half-life and GFR, with the construction of "isoconcentration dosages", by which it is possible to achieve levels similar to those in normal subjects receiving a normal dosage.

Topics: Body Weight; Cefamandole; Cephalosporins; Extracellular Space; Female; Glomerular Filtration Rate; Half-Life; Humans; Kidney Failure, Chronic; Kinetics; Male