title: Pharmacokinetic/pharmacodynamic adequacy of echinocandins against Candida spp. in intensive care unit patients and general patient populations.
abstract: This study evaluated whether contemporary echinocandin regimens achieved pharmacokinetic/pharmacodynamic targets in ICU patients and general patient populations (GPPs) and assessed caspofungin (CAS) regimens in hepatic impairment (HI) patients. A Monte Carlo simulation was performed using previously published data. Recommended dosing regimens of echinocandins in ICU patients, GPPs and healthy volunteers were evaluated: 70mg loading dose then 50mg maintenance dose (70/50mg) for CAS; 100mg q24h for micafungin (MCF); and 200/100mg for anidulafungin (ANF). Moreover, CAS 70mg and 100mg q24h in GPPs, and CAS 70/50mg and 70/35mg in mild and moderate HI patients, respectively, were evaluated. Cumulative fraction of response (CFR) was calculated for each dosing regimen. For Candida albicans, CFRs for the recommended doses of CAS, MCF and ANF were 95.8%, 13.5% and 50.5% in ICU patients and 96.3%, 42.4% and 61.6% in GPPs, respectively; for Candida glabrata, CFRs were 99.4%, 90.6% and 44.6% in ICU patients and 99.5%, 97.1% and 59.8% in GPPs. For Candida parapsilosis, CFRs of echinocandins for standard regimens were <70%; only CAS 100mg q24h achieved the target CFR. CAS 70/50mg and 70/35mg in mild and moderate HI patients were appropriate. Considerable interindividual variability was observed. For C. albicans and C. glabrata, CAS is good choice both for ICU and other patient populations, but for C. parapsilosis an increased dose should be considered. For MCF and ANF, administering higher doses with longer dosing intervals achieves better target attainment and should be investigated in clinical trials.
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: 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: 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: 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: Xiaowei
authors.initials: X
authors.lastname: Zheng
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: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Ti
authors.initials: T
authors.lastname: Meng
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: dongyalin@mail.xjtu.edu.cn.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology*; D054714:Echinocandins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D064368:Healthy Volunteers; D006801:Humans; D007362:Intensive Care Units; D009010:Monte Carlo Method
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins
keywords: Candida; Cumulative fraction of response; Echinocandin; Intensive care unit; Pharmacokinetic/pharmacodynamic