Clinical Pharmacokinetics of Sisomicin: Dosage Schedules in Renal-Impaired Patients

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 m(2)) 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.