Renal handling of the monobactam azthreonam in healthy subjects

Azthreonam is a new completely synthetic, monocyclic beta-lactam antibiotic with potent activity in vitro against most gram-negative aerobic bacteria. Its renal handling was studied in six healthy men after an intravenous loading dose of 1200 mg over 2 min followed by a continuous infusion of 500 mg/hr for 4 hr with and without oral probenecid (1 gm b.i.d. for 2 days before azthreonam infusion and during the day of infusion). To assess glomerular filtration, each subject also received an intravenous loading dose and continuous infusion of inulin. Azthreonam was excreted in the urine by glomerular filtration and tubular secretion in essentially equal proportions. Probenecid reduced plasma clearance of azthreonam bY suppressing renal tubular secretion, without altering glomerular filtration rate or nonrenal elimination. Probenecid increased total and free azthreonam levels and the azthreonam plasma t1/2 while reducing plasma protein binding and the apparent steady-state volume of distribution.