Renal handling of the monobactam azthreonam in healthy subjects

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Abstract
Renal handling of azthreonam was studied in 6 healthy men after an i.v. loading dose of 1200 mg over 2 min followed by a continuous infusion of 500 mg/h for 4 h with and without oral probenecid (1 gm twice daily for 2 days before azthreonam infusion and during the day of infusion). To assess glomerular filtration, each subject also received an i.v. 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 half-life while reducing plasma protein binding and the apparent steady-state volume of distribution.

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