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Population Pharmacokinetic Model-guided Optimization of Intravenous Voriconazole Dosing Regimens in Critically Ill Patients with Liver Dysfunction

Population Pharmacokinetic Model-guided Optimization of Intr...

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2022第27届广东省药师周大会

作者： Xiao-bin Lin ka Yin Lui Peng-hao Guo Xiao-man Liu Tao Liang Xiao-guang Hu Li Tong Jing-jing Wu Yan-zhe Xia Pan Chen Guo-ping Zhong Xiao Chen Chang-jie Cai Department of Pharmacy The First Affiliated HospitalSun Yat-sen University Department of Critical Care Medicine The First Affiliated HospitalSun Yat-sen University Department of Clinical Laboratory The First Affiliated HospitalSun Yat-sen University Institute of Clinical Pharmacology School of Pharmaceutical SciencesSun Yat-sen University

Objectives:This prospective study aimed toestablish a population pharmacokinetic(PPK) model ofintravenous voriconazole(VRC)incritically ill patients with liver dysfunction,andto explore the optimal dosing strategies in specific clinical scenariosfor invasive fungal infections(IFIs)caused by common Aspergillus and Candida ***:The PPK analysis was conducted on 297 plasma VRC concentrations from 26 critically ill patientswith liver ***-based simulations with therapeutic range of 2-6 mg/L as the plasma trough concentration(Cmin) target and the free area under the concentration-time curve from 0 h to 24 h(?AUC24) divided by the minimum inhibitory concentration(MIC)(i.e.?AUC24/MIC) ≥ 25 as the effective target were performed to optimize VRC dosing regimensfor Child-Pugh class AandB(CP-A/B) and Child-Pugh class C(CP-C) ***:A two-compartment model with first-order elimination adequately described the *** covariates in the final model werebody weight onboth central and peripheraldistributionvolumeand Child-Pugh class on *** VRC loading dose of 5 mg/kg every 12 h(q12 h) for the first day was adequate for CP-A/B and CP-C patients to attainthe Cmin target at 24 *** doseregimens of 100 mgq12 h or 200 mgq24 h for CP-A/B patients and 50 mgq12 h or 100 mgq24 h for CP-C patientscould obtain the probability of effective target attainmentof > 90% at an MIC≤ 0.5 mg/L and achieve the cumulative fraction of response of> 90% against ***,***,***,***,***,and ***,the daily VRC dosescould be increased by 50 mg for CP-A/B and CP-C patients at an MIC of 1 mg/L,with plasma Cminmonitoredclosely to avoid serious adverse *** is recommendedthat an appropriate alternative antifungal agent or a combination therapycould be adopted when an MIC ≥ 2 mg/lis reported,or whenthe infection iscaused by *** the MIC valueisnot ***:For criti

关键词： voriconazole population pharmacokinetics dosage optimization liver dysfunction critically ill patients

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