Application Of Voriconazole TDM In Antifungal Treatment And The Influence Of Hypoproteinemia On Voriconazole

1.Application of Voriconazole Therapeutic Drug Monitoring in Anti-fungal Treatment of Respiratory Patients1.1 ObjectiveProspective analysis of the clinical significance of routine voriconazole TDM in patients treated with voriconazole antifungal therapy in the respiratory department.1.2 MethodsA prospective study was performed on 45 patients who were treated with voriconazole in the respiratory department.The patients were divided into CON group and TDM group according to whether or not the steady-state plasma concentration of voriconazole was monitored.The patients in the TDM group were monitored the steady-state plasma trough concentration during voriconazole treatment,and according to the trough concentration to adjust the dose,furthermore,compared the treatment efficiency and incidence of adverse drug events in the two groups of patients.1.3 ResultsCompared with the CON group,the incidence of adverse reactions in the TDM group decreased,but there was no statistical difference?31.82%vs 21.74%,P>0.05?;there was no statistical difference in the treatment efficiency?86.36%vs 86.96%,P>0.05?.The incidence of voriconazole withdrawal caused by adverse events decreased?27.27%vs 4.35%,P=0.048?,the difference was statistically significant.2.The Influence of Hypoproteinemia on Voriconazole2.1 ObjectiveThe plasma concentration of voriconazole was monitored in patients treated with voriconazole to analyze the influencing factors of initial steady-state plasma trough concentration of voriconazole,and the effect of hypoproteinemia on the initial steady-state plasma concentration of voriconazole was analyzed in detail;The formula for the relationship between the initial steady state plasma trough concentration of voriconazole and various factors was established,so that it was possible to predict whether the initial blood drug trough concentration of voriconazole to be within a safe range before administration,so as to prevent the blood concentration from being too high or too low and direct the patient to individualized administration.2.2 MethodsThe plasma concentrations of 49 patients treated with voriconazole were monitored by high performance liquid chromatography.The effects of age,sex,daily dose based on body weight,ALB,ALT,AST,TBIL,DBIL and combination of PPI on blood concentration of voriconazole were analyzed.2.3 ResultsThere was a significant correlation between age,ALB level,AST level and initial plasma trough concentration of voriconazole?P<0.05?;Age>85 years,ALB<35 g/L,DBIL>10?mol/L were important factors influencing the plasma concentration ofpatients?P<0.05?,and they all had statistical difference;The effects of voriconazole daily dose based on body weight,ALT,TBIL,combined PPI,etc.on their plasmaconcentrations were not statistically significant.Differences,but as the index increases,the patient's initial steady-state trough concentration of voriconazole also graduallyincreased;Compared with ALB<35 g/L group,ALB?35 g/L group had lower incidence of adverse reactions and higher total effective rate,and there was significant difference between the two groups?P<0.05?.Multiple stepwise regression analysis showed that ALB was negatively correlated with concentration,while age and AST were positively correlated with the concentration.The regression equation was:Y=2.52+0.054X₁-0.096 X₂+0.018X₃(Y is C_min;X₁ is age;X₂ is ALB level;X₃ is AST level).3.Conclusion3.1 Conventional voriconazole TDM can significantly reduce the incidence of discontinuation due to adverse reactions?P<0.05?.Therefore,TDM monitoring is beneficial for patients treated with voriconazole.3.2 Age,ALB,and AST were significant factors that affected the initial steady-state plasma trough concentration of voriconazole?P<0.05?.Patients with hypoproteinemia had high rates of treatment failure and adverse reactions.It is recommended that patients with hypoproteinemia,especially those with eld or abnormal liver function,be monitored for voriconazole to achieve individualized administration.