Pharmacokinetics of Azlocillin in Subjects with Normal and Impaired Renal Function

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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 (T1/2α) was 0.11 h, and the mean elimination serum half-life (T1/2β) was 0.89 h. The volume of the central compartment (VC) was 7.36 liters/1.73 m2, and the apparent volume of distribution (Vdss) was 14.15 liters/1.73 m2, i.e., 21.9% of body weight. The T1/2β after a 30-min intravenous infusion of 80 mg/kg to the same healthy subjects was 1.11 h. Serum clearances (CS) for the 30- and 80-mg/kg doses were 215.0 and 152.9 ml/min per 1.73 m2. The mean renal clearances (CR) were 145.2 and 94.1 ml/min per 1.73 m2 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 T1/2β values were 2.03, 4.01, and 5.66 h with creatinine clearances (Ccr) within 30 to 50, 10 to 30, and <10 ml/min per 1.73 m2, 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 (T1/2β) and serum creatinine and the elimination rate constant (β) and creatinine clearance (Ccr) provided a basis for adjustment of dosage in renal failure.

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