Pharmacokinetics of high-dose azlocillin sodium in patients with cystic fibrosis.

ABSTRACT

The pharmacokinetics of high-dose azlocillin sodium was studied in 18 patients with cystic fibrosis. Nine male and nine female patients with a mean age of 14.7 years (range 3 to 29 years) participated in the study. They received azlocillin 450 mg/kg/day (as the sodium salt) in six divided doses. During a steady-state dosing interval, a dose of azlocillin was coadministered with a 10-mg/kg dose of iothalamate sodium as a 30-minute infusion. Serum concentrations of azlocillin and iothalamate were determined by high-pressure liquid chromatography assay. The data were analyzed using model-independent methods. The mean elimination rate constant for azlocillin was 0.64 +/- 0.22 hr-1 and the mean serum half-life was 1.22 +/- 0.39 hr. Total clearance of azlocillin, calculated by noncompartmental analysis, was 77.2 +/- 26.4 mL/min/sq m. Glomerular filtration rate, as estimated by measuring iothalamate clearance, was 79.6 +/- 21.9 mL/min/sq m. The total clearance of azlocillin correlated with iothalamate clearance. Patients with cystic fibrosis appear to eliminate azlocillin more rapidly than healthy individuals. This rapid elimination warrants the use of high doses to maintain high serum concentrations.