Jul 24, 1984 - cancer chemotherapy. A third group of seven neutropenic ... treonam pharmacology studies were begun between 24 and. 48 h after the start of ...
Vol. 26, No. 4
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, OCt. 1984, p. 455-461 0066-4804/84/100455-07$02.00/0 Copyright C) 1984, American Society for Microbiology
Clinical Pharmacokinetics of Aztreonam in Cancer Patients PAULA G.
JONES,'*
GERALD P. BODEY,1 EDWARD A. SWABB,2 D. H. W. HO,1 VICTOR JACYR PASTERNAK'
FAINSTEIN,1 AND
Section of Infectious Diseases, Department of Internal Medicine, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030,1 and Department of Clinical Pharmacology, The Squibb Institute for Medical Research, Princeton, New Jersey 085402 Received 9 April 1984/Accepted 24 July 1984
The pharmacokinetics of aztreonam were studied in 25 adult patients with hematological malignancies. Two of nine patients each received aztreonam (1 or 2 g every 8 h) prophylactically, and seven infected patients received a therapeutic regimen of aztreonam (1.5 g every 4 h). The mean peak serum concentration after a 1-g dose of aztreonam (given over 0.5 h on day 1) was 75.5 ,ug/ml; after a 2-g dose it was 177.2 ,ug/ml. The mean peak serum concentration after a 1.5-g dose of aztreonam (given over 2 h on day 1) was 68.5 ,ug/ml. The serum half-life ranged between 1.7 and 2.0 h for all regimens studied. The urinary concentration of the metabolite of aztreonam, SQ 26,992, increased during 1 week of administration of the drug; however, serum levels of the metabolite were barely detectable. groups
Aztreonam is a synthetic monobactam antibiotic, active against aerobic gram-negative bacilli, including multiresistant strains, but not against gram-positive organisms and strict anaerobes (1, 2, 9). In healthy volunteers, aztreonam is eliminated primarily in the urine as unchanged drug and undergoes limited biotransformation to the open beta-lactam ring metabolite, SQ 26,992 (5-8). Single- and multiple-dose pharmacokinetic studies in healthy volunteers have shown serum concentrations of aztreonam after intravenous doses of 0.5, 1, and 2 g that far exceed the MIC for 90% inhibition for members of the Enterobacteriaceae family and isolates of Pseudomonas aeruginosa (5-8). Because of its broad spectrum of activity against gram-negative bacilli, aztreonam may be useful in the treatment of cancer patients. In this study, the pharmacokinetic properties of aztreonam were examined in 25 adult cancer patients who were hospitalized for either the treatment of their primary disease or its complications. MATERIALS AND METHODS Subjects. Twenty-five patients with hematological malignancies were studied. Two groups of patients (nine in each group) received prophylactic aztreonam during week 1 of their hospitalization in a laminar-flow unit, while receiving cancer chemotherapy. A third group of seven neutropenic patients received aztreonam plus vancomycin for treatment of active infections. Informed consent was obtained from all patients according to institutional policies. Patients with known allergies to penicillins or cephalosporins were not eligible for the study. The patients' ages ranged from 16 to 65 years (mean, 46 years). The mean total neutrophil count of the seven patients receiving therapeutic aztreonam was 135 neutrophils per mm3, and that of the 18 patients receiving aztreonam prophylactically was 5,614 neutrophils per mm3. Eligible patients had a serum creatinine of
