title: Population pharmacokinetic analysis of fluconazole to predict therapeutic outcome in burn patients with Candida infection.
abstract: The pharmacokinetic (PK) property of fluconazole might be significantly altered in major burn patients by medical interventions and physiologic changes. In this study, our aims were to investigate fluconazole PK in burn patients using a population approach and to recommend the optimal fluconazole regimen based upon the predicted therapeutic outcome. At steady state, blood samples for PK analysis were obtained from 60 burn patients receiving between 100 and ~400 mg fluconazole daily. A mixed-effect modeling was performed and the therapeutic outcome of antifungal therapy was predicted for 10,000 virtual patients using NONMEM (version 7.2). MIC values were sampled from the MIC distribution at the study site. An area under the free drug concentration-time curve (fAUC)/MIC measurement of >25 h was used as the criterion for therapeutic success. When the same dose was given, the plasma concentration of fluconazole was predicted to be lower in burn patients compared to the nonburn population because of the large PK parameter (clearance, volume of distribution) estimates and continuous renal replacement therapy (CRRT). This tendency was particularly predominant when the patients were within 30 postburn days. Based upon our findings, 400 mg/day fluconazole is recommended to obtain therapeutic successes in major burn patients.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul St Mary's Hospital, The Catholic University of Korea, Seochogu, Seoul, South Korea.
authors.forename: Seunghoon
authors.initials: S
authors.lastname: Han
authors.forename: Jimyon
authors.initials: J
authors.lastname: Kim
authors.forename: Haejun
authors.initials: H
authors.lastname: Yim
authors.forename: Jun
authors.initials: J
authors.lastname: Hur
authors.forename: Wonkeun
authors.initials: W
authors.lastname: Song
authors.forename: Jongtae
authors.initials: J
authors.lastname: Lee
authors.forename: Sangil
authors.initials: S
authors.lastname: Jeon
authors.forename: Taegon
authors.initials: T
authors.lastname: Hong
authors.forename: Heungjeong
authors.initials: H
authors.lastname: Woo
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Yim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002056:Burns / Q000150:complications / Q000382:microbiology*; D002175:Candida / Q000187:drug effects; D002177:Candidiasis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D015725:Fluconazole / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole