Pharmacokinetics of azlocillin in healthy subjects

The pharmacokinetics of azlocillin were investigated in six healthy subjects with normal renal function. 40.4 to 69.6% of the injected dose was recovered, estimated as unchanged form, in urine during 24 h. After intravenous bolus injection of 15 and 30 mg/kg doses, pharmacokinetic data were calculated, using a two-compartment open body model. The mean distribution serum half-life (T1/2 alpha) was 0.11-0.12 h and the mean elimination serum half-life (T1/2 beta) was 0.79-0.89 h. The volume of the central compartment (Vc) was 7.36-8.01 1/1.73 m2 and the apparent volume of distribution (Vdss) was 14.12-14.32 1/1.73 m2. The mean T1/2 beta after a 30 min i.v. infusion of 80 mg/kg to the same healthy subjects was 1.10 h. Serum clearances (Cs) for 15, 30 and 80 mg/kg were 251.1, 214.0 and 152.9 ml/min/1.73 m2 and renal clearance (Cr) were 99.7, 145.2 and 94.1 ml/min/1.73 m2, respectively. Azlocillin pharmacokinetics were found to be dose dependent. Administration of probenecid increased the terminal serum half-life and the total area under the serum azlocillin concentration-time curve and decreased renal clearance, indicating that azlocillin is eliminated by both glomerular filtration and tubular secretion.