title: Population Pharmacokinetics in China: The Dynamics of Intravenous Voriconazole in Critically Ill Patients with Pulmonary Disease.
abstract: Pharmacokinetic research in China on the use of voriconazole in critically ill adult patients with different pulmonary diseases remains to be explored. This study evaluated the population pharmacokinetics of the use of voriconazole (VRC) in critically ill patients to determine covariate effects on VRC pharmacokinetics by NONMEM, which could further optimize VRC dosing in this population. A one-compartment model with first-order absorption and elimination best fit the data, giving 4.28 L/h clearance and 93.4 L volume of distribution of VRC. The model variability, described as an approximate percentage coefficient of interindividual variability in clearance and volume of distribution, was 72.94% and 26.50%, respectively. A significant association between Cmin and drug response or grade 2 hepatotoxicity was observed (p=0.002, <0.001, respectively, 1.5-4.0 µg/mL) via logistic multivariate regression. Monte Carlo simulations at 100, 150, 200, and 250 mg dosage predicted effectiveness at 45.99%, 99.76%, 98.76%, and 67.75% within the 1.5-4.0 µg/mL range, suggesting that a 150 or 200 mg intravenous dose twice daily is best suited to achieve the target steady state trough concentration range in critically ill patients with pulmonary disease.
authors.affiliation: The First Affiliated Hospital of Guangzhou Medical University.
authors.forename: Wenying
authors.initials: W
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.forename: Fenghua
authors.initials: F
authors.lastname: Liang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Meng
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Rui
authors.forename: Xueyan
authors.initials: X
authors.lastname: Yin
authors.forename: Tiantian
authors.initials: T
authors.lastname: Zhang
authors.forename: Xianglin
authors.initials: X
authors.lastname: Xiao
authors.forename: Shaohui
authors.initials: S
authors.lastname: Cai
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Liu
authors.forename: Yimin
authors.initials: Y
authors.lastname: Li
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism; D002681:China; D003198:Computer Simulation; D016638:Critical Illness; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009010:Monte Carlo Method; D065819:Voriconazole / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D065819:Voriconazole