Population Pharmacokinetics of Cefepime in Febrile Neutropenic Patients

호중구감소성 발열 환자에서 Cefepime의 집단 약동학

Background : Cefepime is a broad spectrum cephalosporin that is used for various pathogens including Pseudomonas aeruginosa. Its dosing regimen in Korea has been confined to 2 g q 12 h due to the reimbursement guidelines set for budget containment. To find out scientific guideline for cefepime dosage in Korean patients, knowledge on its population pharmacokinetics is a useful reference. Methods : We recruited 51 febrile neutropenic patients with hematologic malignancy. For the control of their infections, cefepime was given together with other antibiotics. Peak (1-3 h after dosing) and trough (around 6 h after dosing) blood samples per patients were taken for the mixed effect modeling analysis using NONMEM Ver. V. Simulation based upon the population parameters was performed and 500 patients data made up thereafter were tested for the time over MIC (TOM) 2, 4, 8 mg/L. Results : CL was proportional to CLcr, but Vd was not explained by any of the covariates. At the MIC of 2 mg/L, TOM was greater than 40% of dosing interval in all simulated patients. At the MIC of 4 and 8 mg/L, 92% and 67% of the simulated patients had TOM greater than 40% of dosing interval respectively. Discussion : The present study is the first report of population pharmacokinetics of cefepime in febrile neutropenic patients. We expect that this result will be used as a fundamental data for the rational pharmacotherapy of high-cost antibiotics in Korea.