dibekacin and Kidney-Failure--Chronic

Pharmacokinetics of habekacin, a new semisynthetic aminoglycoside antibiotic were investigated in six healthy subjects and twenty-five uraemic patients (six of whom were on hemodialysis) after a single 3 mg/kg Im or IV administration. After the IM injection, the peak serum levels were higher and the times to peak levels were longer in patients with renal impairment than in healthy subjects. Elimination serum half-life increased in relation to the degree of renal impairment, from 2 h in normal subjects to 32 h in patients with creatinine clearance below 10 ml/min. Renal impairment did not significantly modify the apparent volume of distribution. After a single 3 mg/kg dose as one hour-IV infusion in six hemodialysis patients, elimination half-life averaged 48 h and 5 h, out of and on a 4 to 5 hour-hemodialysis session, respectively. Habekacin pharmacokinetic parameters appeared to be similar to those of the other available aminoglycoside antibiotics.

Topics: Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Half-Life; Humans; Infusions, Intravenous; Injections, Intramuscular; Kanamycin; Kidney Failure, Chronic; Renal Dialysis

Dibekacin pharmacokinetics was studied in ten healthy volunteers and six patients with renal failure presenting Clcr less than 10 ml X min-1 per 1.73 m2 of body surface, given as a slow intravenous bolus to the volunteers and as a 30-minute intravenous infusion to the patients. The antibiotic was assayed in plasma and urine by means of a microbiological method using Bacillus subtilis. A two-compartment kinetic model was used to describe the bi-phasic decline of the plasma concentration thus establishing the different pharmacokinetic parameters. Elimination parameters beta, k10 and total body clearance were markedly diminished in renal patients (p less than 0.001): t1/2 beta was 2.0 h, k10 = 0.016 min-1 and Cl = 0.87 ml X min-1 kg body weight in normal subjects and t1/2 beta = 21.4 h, k10 = 0.0011 min-1 and Cl = 0.131 ml X min-1 per kg in the patients. Other kinetic parameters, as distribution (alpha) and transfer (k12, k21) constants were lower in patients than in volunteers. Also the different terms of volume of distribution of the two-compartment model (V1, Vdss, Vdarea) were significantly higher in patients than in normal subjects (p less than 0.05). A good correlation (r = 0.987) between patients' beta constant and creatinine clearance was found. A similar relationship between serum creatinine levels and disposition half-life was found (r = 0.955). Urinary recovery at 24 h was 89.0% of the dose given to normals and 15.8% of the dose given to patients.

Topics: Adult; Creatinine; Dibekacin; Female; Half-Life; Humans; Kanamycin; Kidney Failure, Chronic; Kidney Function Tests; Kinetics; Male; Metabolic Clearance Rate

The pharmacokinetics of habekacin, a new semisynthetic aminoglycoside antibiotic, were investigated in six healthy subjects and 25 uremic patients (six of whom were on hemodialysis) after administration of a single 3-mg/kg dose. Six healthy subjects received the 3-mg/kg dose both intramuscularly (i.m.) and intravenously (i.v.) (1-h infusion). Uremic patients were given the 3-mg/kg dose as an i.m. injection, except for the hemodialysis patients, who received the dose as a 1-h i.v. infusion. After the i.m. injection, the peak concentrations in serum were higher and the times to peak levels were longer in patients with renal impairment than in healthy subjects. The elimination half-life in serum increased in relation to the degree of renal impairment, from 2 h in normal subjects to 32 h in patients with creatinine clearances of less than 10 ml/min. Renal impairment did not significantly modify the apparent volume of distribution. After the same 3-mg/kg dose as a 1-h i.v. infusion in six hemodialysis patients, the elimination half-life averaged 48 and 5 h off and on a 4- to 5-h hemodialysis session, respectively. The habekacin pharmacokinetic data appeared to be similar to those of the other available aminoglycoside antibiotics.

Topics: Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Half-Life; Humans; Injections, Intramuscular; Injections, Intravenous; Kanamycin; Kidney Failure, Chronic; Kinetics; Metabolic Clearance Rate; Middle Aged; Renal Dialysis; Uremia

The pharmacokinetics of dibekacin were studied in 23 patients with varying degrees of renal insufficiency. Creatinine clearance was between 4 and 51 ml/min. Chronic renal insufficiency did not affect maximum serum concentrations, nor the time required to reach a peak level after an intramuscular injection of 1 mg/kg of dibekacin. The maximum concentration was 4 to 5 mcg/ml and the peak obtained within the first hour. Renal insufficiency caused a very marked prolongation in the serum half-life of elimination. This rose from 6 hours in moderate renal insufficiency to 50 hours in a patient with a clearance of a few millilitres. Whatever the degree of renal insufficiency, it should be noted that urinary concentrations remained markedly higher than the MIC of organisms sensitive to the aminoglycoside. Dibekacin is highly dialysable, being virtually totally extracted during a 6 hours dialysis session using a membrane of 1 m2 surface area. An outline of dose adaptations in relation to the degree of renal insufficiency is suggested on the basis of these pharmacokinetic data.

Topics: Adult; Aged; Dibekacin; Female; Humans; Kanamycin; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Renal Dialysis

Topics: Biological Assay; Dibekacin; Half-Life; Humans; Injections, Intramuscular; Kanamycin; Kidney Failure, Chronic; Kinetics; Renal Dialysis