Disposition kinetics of dibekacin in normal subjects and in patients with renal failure

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.