Aztreonam - How It Works

CLINICAL PHARMACOLOGY Single 30-minute intravenous infusions of 500 mg, 1 g, and 2 g doses of aztreonam for injection in healthy subjects produced aztreonam peak serum levels of 54 mcg/mL, 90 mcg/mL, and 204 mcg/mL, respectively, immediately after administration; at 8 hours, serum levels were 1 mcg/mL, 3 mcg/mL, and 6 mcg/mL, respectively ( Figure 1 ).

Single 3-minute intravenous injections of the same doses resulted in serum levels of 58 mcg/mL, 125 mcg/mL, and 242 mcg/mL at 5 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 1 hour.

After identical single intravenous or intramuscular doses of aztreonam for injection, the serum concentrations of aztreonam are comparable at 1 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 aztreonam for injection exceed the MIC90 for Neisseria sp., Haemophilus influenzae , and most genera of the Enterobacteriaceae for 8 hours (for Enterobacter sp., the 8-hour serum levels exceed the MIC for 80% of strains).

For Pseudomonas aeruginosa , a single 2 g intravenous dose produces serum levels that exceed the MIC90 for approximately 4 to 6 hours.

All of the above doses of aztreonam for injection 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 (1.5-2.0) 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.

The dosage of aztreonam for injection should be adjusted accordingly (see DOSAGE AND ADMINISTRATION: Renal Impairment in Adult Patients ).

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 1,100 mcg/mL, 3,500 mcg/mL, and 6,600 mcg/mL within the first 2 hours following single 500 mg, 1 g, and 2 g intravenous doses of aztreonam for injection (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 mcg/mL.

After intramuscular injection of single 500 mg and 1 g doses of aztreonam for injection, urinary levels were approximately 500 mcg/mL and 1,200 mcg/mL, respectively, within the first 2 hours, declining to 180 mcg/mL and 470 mcg/mL in the 6- to 8-hour specimens.

In healthy subjects, aztreonam is excreted in the urine about equally by active tubular secretion and glomerular filtration.

Approximately 60% to 70% of an intravenous or intramuscular dose was recovered in the urine by 8 hours.

Urinary excretion of a single parenteral dose was essentially complete by 12 hours after injection.

About 12% of a single intravenous radiolabeled dose was recovered in the feces.