The kinetics of netilmicin (N-ethyl-sisomicin), an investigational aminoglycoside, have been determined in man following intravenous and intramuscular administration of a dose of 2 mg/kg. After intravenous injection the serum elimination of the antibiotic obeys two-compartment open model kinetics. Distribution and elimination constants are in the range reported for other aminoglycosides, with the exception of the volume of distribution at the steady-state, which appears to be greater than that of sisomicin and of tobramycin. Urinary excretion data suggest that this antibiotic undergoes some degree of tubular reabsorption and appears to be cleared partially by extrarenal processes. After intramuscular administration, the absorption of netilmicin follows first-order kinetics and its physiologic availability is complete.

The pharmacokinetics of intravenously administered sisomicin were studied in 33 patients with normal renal function and different degrees of renal impairment. In all patients, the serum disappearance of sisomicin, once distribution equilibrium had been achieved, followed first-order kinetics and percentage of hourly loss from serum decreased proportionally with decreasing renal function. Half-lives averaged 2.06 h in normal subjects (endogenous creatinine clearance greater than 80 ml/min per 1.73 M2) and reached 35.3 h in a virtually anephric subject. Linear relationships were defined between sisomicin serum half-life and the reciprocal of the endogenous creatinine clearance and serum creatinine concentration. The latter relationship indicates that the half-life of sisomicin may be approximated as twice the serum creatinine concentration and may be used for dosage adjustment in renal-impaired patients. Prediction of the extent of sisomicin removal by hemodialysis may be made from the relationship between the dialyzate of sisomicin and that of creatinine and blood urea nitrogen. Dosage schedules and methods of administration compatible with the pharmacokinetic properties of the antibiotic are finally proposed.

The pharmacokinetics of intravenously administered netilmicin, an investigational aminoglycoside antibiotic, were studied in 38 patients with creatinine clearance ranging from 150 to Oml/min/1.73m2 in order to determine the influence of kidney function status on the disposition of the antibiotic. The serum disappearance of netilmicin followed first order kinetics and the elimination rate constant decreased proportionally with decreasing renal function. Half-lives averaged 2.2 hours in normal individuals (creatinine clearance greater than 80ml/min/1.73m2) and reached 42 +/- 10 hours (mean +/- SD) in virtually anephric patients. The elimination rate constant lowered proportionally with decreasing renal function. Several linear relationships between pharmacokinetic parameters and renal function indicators were defined. A clinically useful correlation indicates that the half-life may be approximated as 3 times the serum creatinine concentration and may be used for adjustment of dosage of netilmicin in the treatment of patients with impaired renal function. During haemodialysis, netilmicin extraction from the blood reaches 75 +/- 14% (mean +-/ 95% confidence interval) of that of creatinine and 88 +/- 19% of that of blood urea nitrogen.