Metabolism and pharmacokinetics of aztreonam in healthy subjects

Swabb, Edward A.; Singhvi, Sampat M.; Leitz, M. A.; Frantz, M; Sugerman, A. Arthur

doi:10.1128/aac.24.3.394

Cited by 68 publications

(25 citation statements)

References 8 publications

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“…administration and 78 and 15%, respectively, after i.m. administration (9). Thus, the renal route of elimination was favored in rats, dogs, and humans, but not in monkeys.…”

Section: Aztreonam ([2s-[2ax3b(z)]]-3-[[(2-amino-4-thiazolyl)-[(l-mentioning

confidence: 91%

Disposition of [14C]aztreonam in rats, dogs, and monkeys

Kripalani¹,

Singhvi²,

Weinstein³

et al. 1984

Antimicrob Agents Chemother

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[14C]aztreonam was administered as single 25-mg/kg doses to dogs (intravenously and subcutaneously) and monkeys (intramuscularly and intravenously) and as single 50-mg/kg doses (intramuscularly and intravenously) to rats. In rats and dogs, radioactive moieties were excreted primarily in urine; in monkeys, they were excreted about equally in urine and feces. Unchanged aztreonam accounted for 77 to 86% of the radioactivity excreted in the urine of rats, dogs, and monkeys; SQ 26,992, the metabolite resulting from hydrolysis of the monobactam ring, accounted for 10 to 15%; and minor, unidentified metabolites accounted for the remainder.In rats with cannulated bile ducts, about 15% of an intramuscular dose was excreted in bile in 24 h; the bile contained a greater percentage of metabolites than that found in urine. In dogs, the apparent elimination halflife of aztreonam in serum was 0.7 h after intravenous administration. Aztreonam and SQ 26,992 accounted for most of the radioactivity in the sera of dogs and monkeys. Serum protein binding of aztreonam and its metabolites ranged from 28 to 35% in dogs and from 49 to 59% in monkeys. In the three species studied, aztreonam was most extensively metabolized in monkeys; SQ 26,992 and other minor metabolites from monkey urine were tested and found to be devoid of any significant antimicrobial activity.Aztreonam ([2S-[2ax,3,B(Z) Fig. 1 Sample collection. Urine from individual rats was collected quantitatively in ice-cooled containers for the sequential intervals ending 4,8, 24, 48, 72, and 96 h after dosing. Feces were collected daily for 4 days. For rats with cannulated bile ducts, bile and urine were collected at frequent intervals for 24 h; feces were collected for 24 h.Blood samples were withdrawn from the jugular veins of dogs at 0.08, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 24, 48, 72, and 96 h after dosing; serum was prepared from each blood sample. Urine was collected in ice-cooled containers for the sequential intervals ending 1,2,3,4,6,8, 24, 48, 72, and 96 h after dosing. Feces were collected daily for 4 days.For monkeys, blood samples were withdrawn from the femoral artery at 0.08 (i.v. only), 0.25, 0.5, 1, 2, 3, 4, 6, 10, and 24 h after dosing; serum was prepared from each blood sample. Urine was collected in ice-cooled containers for the sequential intervals ending 4,8, 24, 48, 72, and 96 h after dosing. Feces were collected daily for 4 days.Additionally, in dogs and monkeys, extra blood samples were withdrawn at 0.25 and 2 h after dosing for the determination of serum protein binding. All

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“…administration and 78 and 15%, respectively, after i.m. administration (9). Thus, the renal route of elimination was favored in rats, dogs, and humans, but not in monkeys.…”

Section: Aztreonam ([2s-[2ax3b(z)]]-3-[[(2-amino-4-thiazolyl)-[(l-mentioning

confidence: 91%

Disposition of [14C]aztreonam in rats, dogs, and monkeys

Kripalani¹,

Singhvi²,

Weinstein³

et al. 1984

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

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“…The metabolism of 3-lactams such as penicillins (2), cefotaxime (1,14), and aztreonam (7,16) (1,2,14,16). Results of this study indicate that the renal clearance of AMA-1294 in rats, which was only by glomerular filtration, is significantly slower than that of carumonam.…”

Section: Distribution (I) Distribution In Erythrocytesmentioning

confidence: 70%

“…and i.v. administration; radioactivity in urine comprised predominantly the unaltered antibiotic, with the remainder consisting of AMA-1294 and unknown metabolites ( A species difference has been recognized in the plasma protein binding of monobactam aztreonam (7,16) and cephalosporins (13). This is also the case for carumonam: the plasma protein binding of carumonam estimated by equilibrium dialysis in humans (18%) (21) occupies an intermediate position between the values for rats (26%) and dogs (8%).…”

Section: Distribution (I) Distribution In Erythrocytesmentioning

confidence: 93%

Disposition of carumonam (AMA-1080/Ro 17-2301), a new N-sulfonated monocyclic beta-lactam, in rats and dogs

Yoshida¹,

Mitani²,

Naeshiro³

et al. 1986

Antimicrob Agents Chemother

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“…No significant differences were found among groups or between the 2-and 4-h sampling times. These values correspond to those found in healthy subjects in a previous study (19 4 -o nonrenal clearance of aztreonam for AC versus both PBC (P o+1+1+ < 0.01) and NC (P < 0.05) groups.…”

Section: Resultsmentioning

confidence: 86%

“…In healthy male subjects given 14C-labeled aztreonam intravenously, 12.3% of the total radioactivity appeared in the feces, reflecting biliary secretion (19). In patients with biliary tract cannulation because of total obstruction of the common bile duct, biliary excretion accounted for a mean of 0.18% of the total administered dose (9).…”

mentioning

confidence: 99%

Effects of cirrhosis on kinetics of aztreonam

MacLeod¹,

Bartley²,

Payne³

et al. 1984

Antimicrob Agents Chemother

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Aztreonam was administered as a single, 3-min, 1-g intravenous infusion to 18 subjects, including 6 with biopsy-proven, primary biliary cirrhosis, 6 with biopsy-proven, stable alcoholic cirrhosis, and 6 age-and sexmatched control subjects with normal hepatic functions. Aztreonam was well tolerated by all subjects. Multiple blood samples and timed, cumulative urine samples were taken for assay of aztreonam content and determination of pharmacokinetic profiles. Protein-free filtrates of serum were also assayed for drug levels. Analyses by microbiological and high-pressure liquid chromatographic procedures gave equivalent results. The kinetic data were described by an open, linear, two-compartment model. There were significant differences in elimination half-life (3.2 verus 1.9 h), serum clearance (0.8 versus 1.1 ml/min per kg), and nonrenal clearance (0.2 versus 0.4 ml/min per kg) between the alcoholic cirrhosis group and the normal control group and in elimination half-life (2.2 versus 1.9 h) between the primary biliary cirrhosis group and the normal control group. There was also a difference in nonrenal clearance between the alcoholic cirrhosis and primary biliary cirrhosis groups (0.2 versus 0.5 ml/min per kg). Although the handling of aztreonam differed in the three groups, the magnitude of the difference would warrant a change in aztreonam dosing only for the alcoholic cirrhosis group. In this group, dose adjustment might be required if long-term therapy with high doses of aztreonam is indicated.

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Metabolism and pharmacokinetics of aztreonam in healthy subjects

Cited by 68 publications

References 8 publications

Disposition of [14C]aztreonam in rats, dogs, and monkeys

Disposition of [14C]aztreonam in rats, dogs, and monkeys

Disposition of carumonam (AMA-1080/Ro 17-2301), a new N-sulfonated monocyclic beta-lactam, in rats and dogs

Effects of cirrhosis on kinetics of aztreonam

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