DISPOSITION KINETICS OF DIBEKACIN IN PATIENTS WITH RENAL-FAILURE AND IN PATIENTS UNDERGOING HEMODIALYSIS

Dibekacin pharmacokinetics was studied in 3 healthy volunteers, 5 pati ents with renal failure presenting Cl-cr, between 4.0 and 67 ml min(-1 ) per 1.73 m(2) 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) meth od. A two compartment kinetic model was used to describe the bi-phasic decline of plasma concentration and to calculate the different pharma cokinetic parameters. Slow disposition and elimination rate constants beta and k(10) respectively, and total body clearance were markedly di minished in anephric patients (p << 0.001):t1/2 beta = 2.12 h, k(10) = 0.642 h(-1) and Cl = 0.882 ml/min per kg, in normal subjects and t1/2 beta = 4.73 h, k(10) = 0.278 h(-1) and Cl = 0.693 ml/min per kg in an ephric 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 0.1 62 to 0.281 l/kg respectively. A good correlation (r = 0.982) between patient's slow disposition constant p and creatine clearance was found . Urinary recovery at 24 h was 85.6% of the dose given to normal volun teers. This value decreased while impairment increased. The mean extra ction coefficient, during hemodialysis was about 0.35.