Single 30-minute intravenous infusions of 500-mg, 1-g and 2-g doses of AZACTAM (aztreonam for injection, USP) in healthy subjects produced aztreonam peak serum levels of 54, 90 and 204 µg/mL, respectively, immediately after administration; at eight hours, serum levels were 1, 3 and 6 µg/mL, respectively (Figure 1). Single 3-minute intravenous injections of the same doses resulted in serum levels of 58, 125 and 242 µg/mL at five minutes following completion of injection.

Serum concentrations of aztreonam in healthy subjects following completion of single intramuscular injections of 500-mg and 1-g doses are depicted in Figure 1; maximum serum concentrations occur at about one hour. After identical single intravenous or intramuscular doses of AZACTAM, the serum concentrations of aztreonam are comparable at one hour (1.5 hours from start of intravenous infusion) with similar slopes of serum concentrations thereafter.

The serum levels of aztreonam following single 500-mg or 1-g (intramuscular or intravenous) or 2-g (intravenous) doses of AZACTAM exceed the MIC90 for Neisseria sp., Haemophilus influenzae and most genera of the Enterobacteriaceae for eight hours (for Enterobacter sp., the eight-hour serum levels exceed the MIC for 80 percent of strains). For Pseudomonas aeruginosa, a single 2-g intravenous dose produces serum levels that exceed the MIC90 for approximately four to six hours. All of the above doses of AZACTAM result in average urine levels of aztreonam that exceed the MIC90 for the same pathogens for up to 12 hours.

When aztreonam pharmacokinetics were assessed for adult and pediatric patients, they were found to be comparable (down to 9-months old). The serum half-life of aztreonam averaged 1.7 hours (1.5 to 2.0) in subjects with normal renal function, independent of the dose and route of administration. In healthy subjects, based on a 70 kg person, the serum clearance was 91 mL/min and renal clearance was 56 mL/min; the apparent mean volume of distribution at steady-state averaged 12.6 liters, approximately equivalent to extracellular fluid volume.

In elderly patients, the mean serum half-life of aztreonam increased and the renal clearance decreased, consistent with the age-related decrease in creatinine clearance.^1-4 The dosage of AZACTAM should be adjusted accordingly

In patients with impaired renal function, the serum half-life of aztreonam is prolonged (See DOSAGE AND ADMINISTRATION: Renal Impairment in Adult Patients.) The serum half-life of aztreonam is only slightly prolonged in patients with hepatic impairment since the liver is a minor pathway of excretion.

Average urine concentrations of aztreonam were approximately 1100, 3500 and 6600 µg/mL within the first two hours following single 500-mg, 1-g and 2-g intravenous doses of AZACTAM (30-minute infusions), respectively. The range of average concentrations for aztreonam in the 8- to 12-hour urine specimens in these studies was 25 to 120 µg/mL. After intramuscular injection of single 500 mg and 1 g doses of AZACTAM, urinary levels were approximately 500 and 1200 µg/mL, respectively, within the first two hours, declining to 180 and 470 µg/mL in the six to eight hour specimens. In healthy subjects, aztreonam is excreted in the urine about equally by active tubular secretion and glomerular filtration. Approximately 60 to 70 percent of an intravenous or intramuscular dose was recovered in the urine by eight hours. Urinary excretion of a single parenteral dose was essentially complete by 12 hours after injection. About 12 percent of a single intravenous radiolabeled dose was recovered in the feces. Unchanged aztreonam and the inactive beta-lactam ring hydrolysis product of aztreonam were present in feces and urine.

Intravenous or intramuscular administration of a single 500-mg or 1-g dose of AZACTAM every eight hours for seven days to healthy subjects produced no apparent accumulation of aztreonam or modification of its disposition characteristics; serum protein binding averaged 56 percent and was independent of dose. An average of about 6 percent of a 1 g intramuscular dose was excreted as a microbiologically inactive open beta-lactam ring hydrolysis product (serum half-life approximately 26 hours) of aztreonam in the zero to eight hour urine collection on the last day of multiple dosing.

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