Pharmacokinetics of two multiple-dose mezlocillin regimens.

The pharmacokinetics of mezlocillin at two dosages were studied over the course of therapy in 12 patients receiving the drug for the treatment of infections. Patients received an initial dosing regimen of 4 g every 6 h or 5 g every 8 h, which was switched to the alternative regimen after 5 days of treatment. Both drug regimens demonstrated similar pharmacokinetic characteristics, which suggests that the reported dose-dependent elimination of mezlocillin is not an important factor in the clinical use of mezlocillin at the dosages currently used.

Pharmacokinetics of aztreonam in patients with gram-negative infections.

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.