Blood Concentration Monitoring Of Voriconazole And Its Analysis On Clinical Rationality ——A Real-world Date Study

Objective:To evaluate the rationality of voriconazole（VRZ）clinical application in a hospital through the study of real world data,analyze the clinical significance of standard load dose and therapeutic drug monitoring（TDM）,and explore the possible influencing factors of blood drug concentration,so as to provide reference for optimizing the clinical application of VRZ.Methods:1.Inpatients receiving VRZ in the First Affiliated Hospital of Anhui Medical University from July 2019 to May 2021 were selected to collect their baseline information,etiological detection,medication status,etc.Evaluation criteria for rational drug use were established according to the instructions and guidelines to evaluate the rationality of VRZ clinical application.2.According to the first-day dose,the patients included in the study were divided into three groups:no loading dose,half loading dose,and the standard loading dose group,The efficacy and safety of the three groups were preliminarily compared,and the no or half loading dose group was further incorporated into the control group.Propensity score matching（PSM）was used to screen patients with baseline balance between control group and standard loading dose group,and the effect of standard loading dose on clinical outcome and compliance rate of blood concentration was analyzed.3.Patients were divided into TDM group and Non-TDM group according to whether or not the trough concentration(C_min)was monitored.PSM was used to select patients with consistent baseline data from the two groups and compare the efficacy and safety of the two groups under different medication purposes.4.Collect relevant information of patients who monitored the C_min,then analyze the relationship between plasma concentration and efficacy and safety,and explore the possible influence of plasma concentration.Results:1.Among 2641 patients using VRZ,there were 2383 patients using VRZ unreasonably,with an irrational rate of 90.23%.The unreasonable forms included improper usage and dosage,drug use without pointer,and inappropriate drug combination,among which no loading dose or insufficient loading dose was particularly prominent.2.According to the intake criteria,A total of 2255 patients were initially enrolled.Before PSM,compared with the other two groups,the standard loading dose group showed no difference in treatment effect.After PSM,a total of 330 patients were enrolled,165 patients in the standard loading dose group and 165 patients in the control group.The standard loading dose was significantly beneficial to the improvement of therapeutic efficacy（83.54%vs 73.33%,P<0.05）,and could increase the compliance rate of plasma concentration（77.63%vs 62.96%,P<0.05）,And it does not increase the risk of adverse drugs reaction（ADR）.3.A total of 516 patients were included in the study after PSM among 2255 enrolled patients,including 258 patients in the TDM group and 258 patients in the Non-TDM group.There was no difference in clinical efficacy between the two groups when preventive medication was used,and the effective rate of TDM group was significantly increased when treatment was used（81.28%vs 71.83%,P<0.05）.The safety assessment showed that TDM group had a significant advantage in reducing the incidence of hepatotoxicity（3.88%vs 8.14%,P<0.05）and the rate of ADR discontinuation（3.49%vs 7.75%,P<0.05）.4.The therapeutic effect of VRZ is closely related to blood drug concentration,and the source of drug,age,liver function index,high-sensitivity C-reactive protein（hs-CRP）,blood lipid,combined glucocorticoid（GC）and calcineurin inhibitor（CNI）are the influencing factors of blood drug concentration.Conclusion:1.The irrational use of VRZ is prominent in clinical practice,so the rationality of drug indication,standardized dosage and combination should be strictly grasped to optimize the clinical application of VRZ.2.If VRZ is not given the standard loading dose,the efficacy and the rate of blood drug concentration reaching the standard will be reduced.Therefore,attention should be paid to the standard loading dose to ensure that more valley concentration falls within the target range,so as to improve the therapeutic effect of VRZ.3.TDM can improve clinical benefits,and it is recommended for patients using VRZ to undergo TDM.4.VRZ varies greatly among individuals,so comprehensive analysis should be conducted according to patients’own physiological and pathological conditions and combined drugs,and individualized treatment plans should be designed based on TDM results to ensure the safety and efficacy of clinical medication.