Dose-dependent pharmacokinetics of azlocillin compared to mezlocillin

The pharmacokinetics of azlocillin at intravenous doses of 1.0, 2.0 and 5.0 g and of 2.0 g mezlocillin were studied in a cross-over study on 10 healthy volunteers. The serum concentrations and total area under the serum curves for azlocillin increased more than expected from the multiples of the dose size. Likewise, the percentage of urinary excretion of an antibacterially active agent increased steadily with higher doses. The same applied to the serum half-life (t 1/2), whereas the total body clearance was reduced. All these characteristics are indicative of dose-dependent, i.e. capacity-limited pharmacokinetics. The t 1/2 was 0.89, 0.98, and 1.53 h for each dose. For 2.0 g mezlocillin, the serum values, urinary recovery, and t 1/2 were lower than the values after the same dose of azlocillin. The t 1/2 was 0.64 h. The total body clearance was 12,0, 9.2, and 6.4 liters/h for the three doses of azlocillin and 14.4 liters/h for 2. g mezlocillin. Dose dependence appears to be more pronounced with azlocillin than found previously with mezlocillin. Unchanged azlocillin and its biotransformation products are excreted more slowly than mezlocillin and its metabolites.