Pharmacokinetics of azlocillin in subjects with normal and impaired renal function.

The pharmacokinetics of azlocillin were investigated in five healthy subjects and in 16 subjects with chronic renal failure. After intravenous bolus injection of a single dose of 30 mg/kg in normal subjects, pharmacokinetic data were calculated, using a two-compartment open body model. The mean distribution serum half-life (T(1/2alpha)) was 0.11 h, and the mean elimination serum half-life (T(1/2beta)) was 0.89 h. The volume of the central compartment (V(C)) was 7.36 liters/1.73 m(2), and the apparent volume of distribution (V(dss)) was 14.15 liters/1.73 m(2), i.e., 21.9% of body weight. The T(1/2beta) after a 30-min intravenous infusion of 80 mg/kg to the same healthy subjects was 1.11 h. Serum clearances (C(S)) for the 30- and 80-mg/kg doses were 215.0 and 152.9 ml/min per 1.73 m(2). The mean renal clearances (C(R)) were 145.2 and 94.1 ml/min per 1.73 m(2) for the respective doses. Between 61.8 and 69.6% of the injected dose was recovered in urine during the first 24 h. The elimination half-life in subjects with chronic renal impairment increased with the degree of renal insufficiency. After a 30-min intravenous infusion of 80 mg/kg the T(1/2beta) values were 2.03, 4.01, and 5.66 h with creatinine clearances (C(cr)) within 30 to 50, 10 to 30, and <10 ml/min per 1.73 m(2), respectively. Urinary elimination was inversely related to the degree of renal impairment. In four patients out of and on a 6-h hemodialysis session mean elimination half-life values were 6.53 and 2.81 h, respectively. The fraction of drug removed by dialysis was 45.8%. The linear relationships between the elimination of half-life (T(1/2beta)) and serum creatinine and the elimination rate constant (beta) and creatinine clearance (C(cr)) provided a basis for adjustment of dosage in renal failure.