Pharmacokinetics of netilmicin in the presence of normal or impaired renal function

Abstract

A pharmacokinetic study of netilmicin was conducted in 12 healthy subjects and 24 subjects with chronic renal failure. After intramuscular administrations of 2 and 3 mg of netilmicin per kg in normal subjects, the mean peak serum concentrations were 5.46 and 8.83 mug/ml, respectively. After intravenous infusions of identical doses, the mean maximum serum levels, occurring at the end of the infusion, were 11.79 and 15.75 mug/ml, respectively. The pharmacokinetic data were very similar via the two routes of administration and for the two doses. The elimination half-life was 2.20 h, and 80 to 90% of the injected dose was recovered in urine during the first 24 h. After intramuscular administration of 2 mg/kg in subjects with chronic renal impairment, the elimination half-life increased to 29.48 h, and urinary elimination was inversely related to the degree of impairment. A study was conducted throughout hemodialysis sessions: serum concentrations decreased by 63.3%. The linear relationships between the elimination rate constant and creatinine clearance and the elimination half-life and serum creatinine allowed us to establish dosage schedules according to the degree of renal failure.