Serum concentration,
biological half-life, distribution space and serum clearance of
sisomicin, a new
aminoglycoside antibiotic, have been studied in twenty-three patients in comparison with the pharmacokinetics of 125I-labelled
iothalamate, a compound only filtered by the kidney. 10 patients had normal or borderline abnormal serum
creatinine (less than 1,5 mg/100 ml), 8 had various degrees of
renal insufficiency (serum
creatinine 1.7-9.6 mg/100 ml) and 6 were being treated by intermittent haemodialysis. After
intravenous injection of
sisomicin 1 mg/kg
body weight in patients with normal or borderline renal function its half-life was 3.5 h, very similar to that of
iothalamate, 3.2 h. The mean distribution space was 20.1% per cent of
body weight;
iothalamate, 23.7%. In patients with
renal insufficiency there was a positive correlation between serum
creatinine level and the half-life of
sisomicin, and an even stronger correlation between the clearances of
iothalamate and
sisomicin. In patients dependent on haemodialysis, the mean serum half-life between dialysis was 40 h, compared to approximately 100 hours for
iothalamate, which implies additional extrarenal clearance or tubular secretion of
sisomicin. The results of pharmacokinetic studies indicated that a regime of
sisomicin 1 mg/kg every 8 to 12 hours in patients with normal renal function would result in serum and urine levels sufficiently high to treat most
urinary tract infections. In patients with impaired renal function the dosage interval should be increased according to the serum
creatinine level, and in patients dependent on haemodialysis one standard dose at the end of each dialysis period should suffice. 9 patients with a chronic
urinary tract infection severely complicated by an underlying disease were treated according to this dosage regimen with a satisfactory bacteriological and clinical result. No adverse reactions or signs of accumulation were observed.