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

Abstract

Dibekacin pharmacokinetics was studied in ten healthy volunteers and six patients with renal failure presenting Clcr<10ml.min-1 per 1.73m2 of body surface, given as a low intravenous bolus to the volunteers and as 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 β, k10 = 0.016 min-1 and Cl = 0.87 ml.min-1 kg body weight in normal subjects and t1/2β = 21.4 h, k10 = 0.0011 min-1 and Cl = 0.131 ml.min-1 per kg in the patients. Other kinetic parameters, as distribution (α) 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 patient than in normal subjects (p<0.05). A good correlation (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.