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Pharmacokinetics and Clinical Response in Patients With Cystic Fibrosis

Adriano G. Arguedas, MD; Harris R. Stutman, MD; Margaret Zaleska, RN; Catherine A. Knupp, DVM, MS; Melvin I. Marks, MD; Eliezer Nussbaum, MD

Am J Dis Child. 1992;146(7):797-802.

Abstract
• Objective.
—To measure first-dose and steady-state plasma, urine, and sputum concentrations of cefepime and make preliminary assessments of the clinical efficacy of cefepime in patients with cystic fibrosis.

Design.
—Open noncomparative clinical trial.

Setting.
—Memorial Miller Children's Hospital of Long Beach, Calif.

Participants.
—Twelve patients, aged 4 to 41 years, with a confirmed diagnosis of cystic fibrosis and chronic bronchopulmonary infections.

Interventions.
—Patients received cefepime at 50 mg/kg per dose (maximum dose, 2 g per dose) given intravenously every 8 hours. Clinical evaluations, pulmonary function tests, quantitative sputum cultures, and sensitivity testing were performed before, at the end of, and 2 weeks after therapy.

Measurements and Main Results.
—Mean (±SD) peak plasma concentrations after the first dose were 148.2 (36.6) mg/L; the following other values were included: half-life, 1.59 (0.46) hours; area under the curve, 292 (94) µg/h per milliliter; total-body clearance, 3.01 (1.46) mL/min per kilogram; volume of distribution at steady state, 0.32 (0.10) L/Kg; and percent of dose recovered in urine, 52% (27%). Steady-state and first-dose values were similar. Trough levels varied from 6.4 to 7.2 mg/L. Mean (±SD) sputum concentrations at steady state varied from 6.3 (5.4) to 4.8 (2.3) mg/L. At completion of therapy, nine of 10 patients' conditions were improved as indicated by clinical scores (>10 points), forced vital capacity (>10%), and a greater than or equal to 1 log decrease in sputum bacterial concentration. Cefepime was well tolerated in 10 patients, but rash and light-headedness developed in two patients. Pseudomonas aeruginosa minimum inhibitory concentration₉₀ increased from the start (64 mg/L) to the end of therapy (256 mg/L) and was unchanged 2 weeks later.

Conclusion.
—Based on these data and the potential advantage of a single agent for the treatment of mixed infections (Staphylococcus aureus and P aeruginosa), comparative clinical trials of cefepime and standard therapy for bronchopulmonary exacerbations in patients with cystic fibrosis appear to be warranted.

(AJDC. 1992;146:797-802)

Author Affiliations
From the Pediatric Infectious Disease (Drs Arguedas, Stutman, and Marks and MS Zaleska and Pediatric Pulmonary (Dr Nussbaum) Divisions, Memorial Miller Children's Hospital, Long Beach, Calif; the Department of Pediatrics, University of California, Irvine (Drs Arguedas, Stutman, Marks, and Nussbaum); and Bristol-Myers Squibb, Wallingford, Conn (Dr Knupp). Dr Arguedas is now with the Infectious Disease Department, National Children's Hospital, San José, Costa Rica.

Footnotes
Accepted for publication March 10, 1992.

Reprint requests to Memorial Miller Children's Hospital, 2801 Atlantic Ave, Long Beach, CA 90801-1428 (Dr Stutman).

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