Disposition kinetics of dibekacin in patients with renal failure and in patients undergoing hemodialysis

Abstract

Dibekacin pharmacokinetics was studied in 3 healthy volunteers, 5 patients with renal failure presenting Clcr, between 4.0 and 67 ml min-1 per 1.73 m2 of body surface and 5 anephric patients given as a 30 minute intravenous infusion. The antibiotic was assayed in plasma and urine by means of a high performance liquid chromatography (HPLC) method. A two compartment kinetic model was used to describe the bi-phasic decline of plasma concentration and to calculate the different pharmacokinetic parameters. Slow disposition and elimination rate constants beta and k10 respectively, and total body clearance were markedly diminished in anephric patients (p << 0.001): t1/2 beta = 2.12 h, k10 = 0.642 h-1 and Cl = 0.882 ml/min per kg, in normal subjects and t1/2 beta = 4.73 h, k10 = 0.278 h-1 and Cl = 0.693 ml/min per kg in anephric patients. The apparent volumes of distribution increased while the creatinine clearance of the patients decreased. Thus Vd(area) of volunteers with normal renal function was statistically significantly lower than that of anephric patients (p < 0.001), from a value of 0.162 to 0.281 l/kg respectively. A good correlation (r = 0.982) between patient's slow disposition constant beta and creatine clearance was found. Urinary recovery at 24 h was 85.6% of the dose given to normal volunteers. This value decreased while impairment increased. The mean extraction coefficient, during hemodialysis was about 0.35.