Comparative pharmacokinetics of lividomycin, amikacin and sisomicin in normal subjects and in uraemic patients

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Abstract
The present study was designed to determine the pharmacokinetics of three new aminoglycoside antibiotics in normal subjects and in uraemic patients. After a single intramuscular injection of 350 mg of lividomycin, 7 mg/kg amikacin or 1 mg/kg sisomicin, the serum half-life (T½) in normal subjects was between 1·74 and 2·23 h and the total elimination constant (Kc) between 0·312 and 0·400 h−1. In patients with renal insufficiency T½ was prolonged as renal function decreased. Patients with very severe uraemia and creatinine clearances (Ccr)T½ of between 40·20 to 56·98 h. Thirty to sixty-four per cent of an injected dose was removed during 8-h haemodialysis using a Cöil dialyser. Urinary excretion during the first 24 h after injection was 80 to 85% in normal subjects, 60% in patients with Ccr between 20 and 80 ml/min and 30% in patients with Ccr between 5 and 20 ml/min. T½ in the uraemic patients was 3 to 5 times the serum creatinine level and we therefore suggest 2 dose schedules: a full dose every 3 T½ or a reduced sustaining dose related to creatinine clearance.

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