A pharmacokinetic evaluation of concomitant administration of linezolid and aztreonam

Linezolid, a new oxazolidinone antimicrobial agent, has a spectrum of activ ity encompassing a wide variety of Grampositive bacteria. The purpose of th is study was to evaluate the pharmacokinetics of linezolid and aztreonam, a n antimicrobial agent with selective activity against Gram-negative bacteri a, when given alone and in combination. Healthy subjects were randomized to receive single, 30-minute intravenous infusions of (1) linezolid 375 mg (2 ) aztreonam 1000 mg, and (3) linezolid 375 mg plus aztreonam 1000 mg in an open-label, crossover manner. The only statistically significant difference s observed with combination treatment relative to each drug alone were an i ncrease in the maximum plasma concentration of linezolid (similar to 18%) a nd an approximate 7% decrease in the apparent elimination rate of aztreonam , neither of which are expected to be clinically significant. In healthy su bjects, the combination of linezolid and aztreonam was safe and well tolera ted compared with each agent used alone. Pharmacokinetic data demonstrate t hat coadministration of linezolid and aztreonam does not alter the disposit ion of either agent under single-dose conditions. Therefore, it is not expe cted that a dose alteration of either agent will be necessary in a clinical setting. (C) 1999 the American College of Clinical Pharmacology.