Pharmacokinetics of sisomicin in the presence of normal and impaired renal function

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The pharmacokinetic data of sisomicin, a new aminoglycoside antibiotic, were studied in ten normal subjects and in 24 uremic patients with various degrees of renal insufficiency. All subjects received a single dose of 1 mg/kg intramuscularly. Serum and urine levels were determined using a modification of the agar diffusion method with Bacillus subtilis as test organism. In normal subjects, the mean peak level was 4.54 ± 0.80 mcg/ml and the serum half-life (t/2) 2.27 ± 0.22 h. The apparent volume of distribution was 14.5 ± 2.3 1/1.73 m2, i.e. 22.7 ± 3.2% of body weight. 85.2 % ± 9.5 % of the injected dose was excreted in the urine during the 24 hours following injection. Renal clearance was 67.0 ± 14.9 ml/min/1.73 m2, i.e. 54.4 % ± 10.2 % of creatinine clearance (Ccr). In uraemic patients, the mean peak level was between 5.01 ± 0.65 and 5.59 ± 1.17 mcg/ml. We observed a very sharp increase in t/2 when creatinine clearance fell below 30 ml/min. Compared to 2.27 h in normal subjects, t/2 was 8 h in patients with 20<Ccr<80 ml/min (Group I), 22.61 h in patients with 5<Ccr<20 ml/min (Group II) and 56.98 h in patients with very poor renal function (Ccr<5 ml/min) (Group III). The urinary excretion of sisomicin diminished as the renal function decreased: 70 % of the injected dose in Group I and 44 % in Group II was excreted during the 48 hours following injection. In haemodialysed patients, 27.8–53 % of the sisomicin was extracted during a six hour dialysis session. On the basis of these pharmacokinetic data, it is possible to establish dosage schedules adapted to the degree of renal impairment.