CEFEPIME PHARMACOKINETICS IN CYSTIC-FIBROSIS

Study Objective. To determine the disposition of cefepime in patients with cystic fibrosis compared with healthy controls. Design. Open-labe l, single-dose study. Setting. Laboratoire de Pharmacocinetique Cliniq ue, Universite Laval, Quebec, Canada. Patients and Subjects. Twelve pa tients with the confirmed diagnosis of cystic fibrosis (CF) and 12 hea lthy volunteers. One subject with CF withdrew for personal reasons; th e data of another patient were excluded from the evaluation of renal v alues due to incomplete urine collection. Interventions. A single 2000 -mg dose of cefepime was administered as a 30-minute intravenous infus ion. Healthy subjects did not use any other drugs throughout the study . Those with CF refrained from taking prophylactic antibiotics prior t o and during the study, but continued to use pancreatic enzymes, multi vitamins, and beta-agonist and/or steroid inhalers. One patient contin ued insulin treatment. Measurements and Main Results. Cefepime's maxim um concentration was approximately 150 mug/ml at the end of the infusi on, half-life 2-2.5 hours, and urinary recovery 80% in both groups. No statistically significant difference was seen in any of the pharmacok inetic values between the groups, except for the mean residence time ( 2.03 +/- 0.26 vs 2.39 +/- 0.37 hrs; p<0.02). Total clearance was 19% h igher in patients with CF than in healthy volunteers (119.7 +/- 20.1 v s 103.5 +/- 19.8 ml/min), perhaps due to higher renal (95.1 +/- 12.4 v s 85.1 +/- 12.0 ml/min) and/or nonrenal (25.4 +/- 13.1 vs 18.4 +/- 12. 0 ml/min) clearances in subjects with CF. Conclusions. The disposition of cefepime is not significantly affected by CF, and dosage adjustmen t appears not to be necessary in these patients.