Pharmacokinetics of aztreonam in patients with gram-negative infections

Abstract

Aztreonam pharmacokinetics were assessed in seven patients treated for urinary (n = 6) or lower respiratory (n = 1) tract infections. Each patient was studied twice, at the beginning and end of therapy (7 to 10 days). The patients enrolled had normal to moderately impaired renal function; a good correlation (r2 = 0.90) between serum aztreonam clearance (CL) and creatinine clearance (CLCR) was observed (mean CL/CLCR ratio = 1.11). CL ranged from 21.6 to 121 ml/min per 70 kg, and the half-life ranged from 1.6 to 8.9 h. The mean steady-state volume of distribution (0.16 +/- 0.05 [standard deviation] liter/kg) approximated the extracellular fluid volume. Protein binding of aztreonam in serum (mean, 30%) was lower than that reported in healthy adults. CL increased significantly from the first to the last day of the study, probably reflecting increasing renal function. After multiple dosing (1 g every 8 h), no significant accumulation of aztreonam was observed. Overall, the disposition of aztreonam is comparable in infected and noninfected subjects, and dosing adjustments in patients with renal impairment should be facilitated by the good correlation between CL and CLCR.