Metabolism and pharmacokinetics of aztreonam in healthy subjects

Abstract

The metabolism and pharmacokinetics of aztreonam (SQ 26,776) were studied in four healthy male volunteers, each of whom received single 500-mg intravenous and intramuscular doses of 14C-labeled drug according to a two-way crossover design. Serial samples of serum, urine, and feces were assayed for aztreonam and metabolites. Serum pharmacokinetics of aztreonam administered intravenously were described by an open, linear, two-compartment kinetic model. Kinetics of intramuscular aztreonam followed a one-compartment model with first-order absorption and elimination. Intramuscular bioavailability was 100%. After either intravenous or intramuscular administration, aztreonam was eliminated primarily by urinary excretion of unchanged drug (about 66% of dose), whereas only 1% of the dose was found as unchanged drug in the feces, presumably owing to biliary secretion. The average elimination half-life of aztreonam was 1.6 and 1.7 h, respectively, for intravenous and intramuscular administration. Aztreonam did not undergo extensive metabolism; the most prominent biotransformation product of aztreonam was SQ 26,992, the compound resulting from the hydrolytic opening of the beta-lactam ring. Urinary and fecal SQ 26,992 constituted 7 and 3% of the administered dose, respectively. SQ 26,992 was eliminated at a considerably slower rate than was aztreonam.