hr-810 and Kidney-Diseases

Cefpirome is a new broad-spectrum beta-lactam antibiotic that exhibits minimal concentration dependent killing and produces prolonged postantibiotic effects only with Staphylococcus aureus. These pharmacodynamic characteristics suggest that the goal of optimal dosing regimens for cefpirome is to provide serum levels above the MIC of infecting pathogens for most of the dosing interval. Cefpirome has a half-life of 2.0 hours in normal volunteers that increases to 3.1 to 4.4 hours in elderly patients. Serum concentrations following 0.5, 1.0 and 2.0 grams of cefpirome are above the MIC of common pathogens for more than half of the dosing interval. For many of the Enterobacteriaceae, serum concentrations are above the MIC for over 12 hours. The drug distributes primarily into extracellular fluid and does provide potentially therapeutic concentrations in cerebrospinal fluid (CSF). The drug is eliminated primarily by the kidney and requires dosage modification when the creatinine clearance is below 50 ml/min. The half-life of the drug is not significantly altered in patients with cystic fibrosis and hepatic dysfunction. The integration of the drug's pharmacokinetic and pharmacodynamic characteristics support the use of a 12-hour dosing interval for the treatment of serious infection.

Topics: Adult; Age Factors; Aged; Bacteria; Cefpirome; Cephalosporins; Cystic Fibrosis; Drug Administration Routes; Drug Administration Schedule; Humans; Infections; Kidney Diseases; Liver Diseases; Middle Aged

The pharmacokinetic parameters of cefpirome (HR 810) were examined in 22 patients with different degrees of renal impairment. HPLC was used to analyze samples of blood and urine for cefpirome; and enzymatic assay of creatinine in serum and urine was used to assess kidney function. Creatinine clearance correlated linearly with both total and renal clearance of cefpirome. The loss of kidney function resulted in a decreased renal clearance, whereas the volume of distribution remained the same. This result led to an increase in the terminal half-life of the drug, from 2 hours in healthy subjects to 14 1/2 hours in patients with uremia. This increase also resulted in a prolonged high serum concentration well above the minimum inhibitory concentration. The following dosages are thus recommended: (1) creatinine clearance greater than 50 ml/min: normal daily dose, (2) creatinine clearance from 20 to 50 ml/min: 50% of normal daily dose, and (3) creatinine clearance less than 20 ml/min: 25% of normal daily dose. An initial loading dose of 1 gm, independent of renal function, is advised. Cefpirome was safe and well tolerated.

Topics: Adult; Aged; beta 2-Microglobulin; Cefpirome; Cephalosporins; Creatinine; Drug Tolerance; Female; Half-Life; Humans; Kidney Diseases; Male; Metabolic Clearance Rate; Middle Aged

The pharmacokinetics of cefpirome (CPR), a new injectable cephem, were studied in 9 patients with various degrees (classified by Ccr.) of impaired renal function. Serum and urinary concentrations of CPR were measured by bioassay. The pharmacokinetic analyses were based on a two compartment open model. As renal impairment increased, higher serum concentrations were maintained in beta-phase and higher urinary concentrations were kept over a long time, as well. As a conclusion, it is necessary to consider the adequate administration and dosage for patients with renal impairment to prevent side effects caused by the maintenance of cefpirome in serum over a long time.

Topics: Aged; Cefpirome; Cephalosporins; Female; Humans; Kidney; Kidney Diseases; Male; Middle Aged

Effects of cefpirome (CFP, HR 810; CAS 84957-29-9) and other cephalosporins such as cefotaxime (CFX), cephaloridine (CPH) and ceftazidime (CFZ) on the renal biochemical processes such as peroxidation of lipids, organic cation transport or gluconeogenesis were investigated in vitro or after i.v.-administration of cephalosporins to 200 g male Wistar rats. In a series of in vitro experiments renal cortical slices were incubated for 60 min in a cephalosporin free medium or in a cephalosporin containing medium (1.25, 2.5, 5.0 and 10 mg/ml) at 37 degrees C under a 100% O2 atmosphere. Subsequently, peroxidation of lipids (LPO), measured as malondialdehyde (MDA) production, tissue accumulation of the organic cation tetraethylammonium (TEA) and gluconeogenesis were determined. In one series of in vivo experiments, 2 h after i.p.-administration of saline, CFP, CFX, CPH and CFZ (0, 500, 1000 and 2000 mg/kg), rats were killed and the amount of the reduced glutathione (GSH) in the renal cortex was measured. In another series of experiments, CFP, CFX, CPH and CFZ were administered (1200 mg/kg/d, i.v.) for 5 days. Subsequently, the effects of these cephalosporins on MDA production, cytosolic lactate dehydrogenase (LDH) activity, TEA accumulation and gluconeogenesis in the renal cortex were investigated. Results of the in vitro experiments show a significant concentration-dependent increase in MDA production only after incubation of renal cortical slices with CPH. CFZ and CPH caused a dose-dependent decrease in gluconeogenesis and except CFX, all other investigated cephalosporins induced a dose-dependent decrease in TEA accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cefotaxime; Cefpirome; Cephalosporins; Cytosol; Gluconeogenesis; Glutathione; In Vitro Techniques; Kidney Cortex; Kidney Diseases; L-Lactate Dehydrogenase; Male; Malondialdehyde; Oxidation-Reduction; Rats; Rats, Inbred Strains; Tetraethylammonium; Tetraethylammonium Compounds