The Impact of Plasma Protein Binding Characteristics and Unbound Concentration of Voriconazole on Its Adverse Drug Reactions

Overview

Journal Front Pharmacol

Date 2020 May 12

PMID 32390847

Citations 13

Authors

Zi-Qing-Yun Yuan

Chun Qiao

Zhi-Cheng Yang

Lei Yu

Lu-Ning Sun

Yi Qian

Xue-Hui Zhang

Ling Meng

Xiao-Yan Zhang

Yong-Qing Wang

Affiliations

Soon will be listed here.

Abstract

This study investigated voriconazole (VRC) unbound plasma concentration and its relationship with adverse drug reactions (ADRs) in patients with malignant hematologic disease. Plasma samples were collected from patients or spiked . A time-saving rapid equilibrium dialysis assay was used for the separation of unbound and bound VRC, following a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis method for drug concentration detection. Liver function and treatment details were collected from the electronic medical records of patients. Protein concentration was determined according to instructions. VRC plasma protein binding rate (PPB) in patient is significantly higher [69.5 ± 6.2%] than that in in-vitro samples, influenced by total drug concentration (C), plasma protein concentration, and protein type. The α1-acid glycogen (AAG) has the highest affinity with VRC. Relationship between total PPB of VRC with PPB of individual protein is not a simple addition, but a compressive combination. Unbound drug concentration (C) of VRC shows significant relationships with C, protein concentration, AST level, metabolism type of CYP2C19 and co-administration of high PPB medicines. Unbound plasma concentration of VRC shows a more sensitive relationship with ADRs than C.

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