Pharmacokinetics of Azlocillin in Subjects with Normal and Impaired Renal Function

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Abstract
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 1/2α ) was 0.11 h, and the mean elimination serum half-life (T 1/2β ) 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 1/2β 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 1/2β values were 2.03, 4.01, and 5.66 h with creatinine clearances ( C cr ) within 30 to 50, 10 to 30, and 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 1/2β ) and serum creatinine and the elimination rate constant (β) and creatinine clearance ( C cr ) provided a basis for adjustment of dosage in renal failure.