Pharmacokinetics of intravenously administered tobramycin in normal volunteers and in renal-impaired and hemodialyzed patients

Abstract

The pharmacokinetics of intravenously administered tobramycin, an aminoglycoside antibiotic, were studied in 16 volunteers with normal renal function and 10 patients with different degrees of renal impairment. In all subjects, the disappearance of tobramycin from serum followed first-order kinetics, and the elimination rate constant decreased proportionally with increasing degree of renal impairment. The half-life average 82 min in normal subjects (endogenous creatinine clearance, greater than 80 ml/1.73 m2 per min) and was 33.7 hr in a totally anephric subject. Linear relations were defined between the half-life of tobramycin in serum and the reciprocal of the endogenous creatinine clearance and between the half-life of the drug and the concentration of serum creatinine. These relations may be used for dosage adjustment in patients with renal impairment. In hemodialyzed patients, the half-life decreased six- to ninefold during dialysis for 6 hr. The extent of tobramycin elimination by hemodialysis may be predicted from relations established between the elimination of tobramycin and that of creatinine and blood urea nitrogen. Dosage schedules must be compatible with the pharmacologic and pharmacokinetic properties of the antibiotic.