title: Optimization of voriconazole dosage regimen to improve the efficacy in patients with invasive fungal disease by pharmacokinetic/pharmacodynamic analysis.
abstract: Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in hospitalized patients. To maximize the efficacy of voriconazole treatment, the study established the relationship between voriconazole pharmacokinetic/pharmacodynamic (PK/PD) and probability of response and optimized voriconazole dosage regimen in patients with IFD based on Monte Carlo simulation. Forty-four patients proven with IFD were involved in this study. Among them, the overall cure rate was 75% (33/44) and there was a significant difference between Cmin /MIC values in patients with lack of response (n = 11) and those with successful response (n = 33) (mean value: 1.91 vs. 11.33; P < 0.05). Logistic regression model showed a high correlation between voriconazole Cmin /MIC ratio and clinical response (P = 0.044, OR = 1.349). According to Monte Carlo simulation results under different voriconazole dosing regimens, we could draw a conclusion that 200 mg voriconazole administered intravenously or orally twice daily for Candida infections and 300 mg administered orally or with 200 mg administered intravenously twice daily for Aspergillus infections were rational, which could achieve a value of the cumulative fraction of response >90%. This study built the relationship between voriconazole PK/PD and clinical response and obtained the reasonable empirical dosage regimen, which can be used to customize individual dosage regimen and improve the efficacy of voriconazole treatment.
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Taotao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Qianting
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Jin'e
authors.initials: J
authors.lastname: Lei
authors.affiliation: Central Intensive Care Unit, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China. dongyalin@mail.xjtu.edu.cn, dongyalin@medmail.com.cn.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China. dhy260113@sina.cn.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Dong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001230:Aspergillus / Q000187:drug effects / Q000302:isolation & purification; D002176:Candida albicans / Q000187:drug effects / Q000302:isolation & purification; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000072742:Invasive Fungal Infections / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D009010:Monte Carlo Method; D016896:Treatment Outcome; D065819:Voriconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D065819:Voriconazole
keywords: Cmin/MIC; Monte Carlo simulation; efficacy; invasive fungal disease; voriconazole