Effect Of Hypoproteinemia On Antifungal Efficacy And Trough Concentration Of Voriconazole

OBJECTIVE:Therapeutic drug monitoring（TDM）was performed in hypoproteinemic patients using voriconazole to investigate the clinical significance of voriconazole TDM in hypoproteinemic patients,to explore the factors affecting the trough concentration(C_min)of voriconazole in hypoproteinemic patients,and to assess the relationship between C_minof voriconazole and efficacy and ADR in hypoproteinemic patients to improve the antifungal efficacy of voriconazole.METHODS:1.A retrospective analysis was used to monitor the dosing of patients using voriconazole from November 2016 to March 2021,and patients were divided into hypoproteinemic（HAE）and non-hypoproteinemic patients（N-HAE）groups according to their albumin concentration,and the differences in C_minof voriconazole and related variables between the two groups were analyzed to compare the efficiency of voriconazole treatment and the incidence of ADR.2.To analyze the initial steady-state blood C_minof voriconazole in 49 patients with hypoproteinemia admitted to the hospital from November 2016 to August 2021,and to analyze the effect of 10 variables,including gender,age,voriconazole body weight daily dose,combined proton pump inhibitor,CRP,ALT,AST,DBIL,TBIL,and ALB,on C_minof voriconazole and to evaluate C_minof voriconazole in patients with hypoproteinemia in relation to efficacy and adverse effects.RESULTS:1.Forty-five and twenty patients with HAE and N-HAE were included,respectively,and the mean C_minand C_min>5.5 mg·L^-1rates of voriconazole were significantly higher in the HAE group(4.92±3.78 vs 2.61±1.69 mg·L^-1P=0.003;31.1%vs5.0%P=0.037)and the treatment recovery rate was significantly lower in the HAE group compared with the N-HAE group（33.3%vs 60.0%P=0.044）and a significantly higher incidence of liver injury（42.22%vs 5.00%P=0.003）;with C_minof voriconazole>5.5 mg·L^-1,HAE patients were significantly more likely to be abnormal in C-reactive protein（CRP）and glutamate transaminase（AST）than N-HAE patients（P<0.05）.2.A total of forty-nine HAE patients were included,and C_minof voriconazole was positively correlated with CRP and AST and negatively correlated with ALB（P<0.05）;CRP≥100 mg·L^-1,DBIL>10 Umol·L^-1,and AST>40 U·L^-1were significant factors affecting C_minof voriconazole in HAE patients（P<0.05）;whereas voriconazole weight daily dose,age,gender,co-administered PPI,ALT,and TBIL had no significant effect on C_minof voriconazole in the HAE cohort（P>0.05）;the incidence of adverse reactions was significantly lower in patients with C_minof voriconazole within 1-5.5 mg·L^-1compared to those with C_minof voriconazole>5.5 mg·L^-1（P<0.05）;stepwise multivariate linear regression model showed that CRP and TBIL were positively correlated with C_minof voriconazole in patients with HAE（P values 0.014 and 0.029,respectively）,and subject operating characteristic（ROC）curve analysis showed that CRP concentrations≧106.85 mg·L^-1increased the incidence of C_minof voriconazole greater than 5.5 mg·L^-1.（95%CI=0.626～0.958,P=0.003）.CONCLUSION:Patients with hypoproteinemia had significantly higher C_minof voriconazole,a significantly higher incidence of liver injury,and a correlation between CRP levels and C_minof voriconazole.Patients with hypoproteinemia should be closely monitored for C_minof voriconazole and CRP levels,which in turn can help improve voriconazole efficacy by adjusting the dose of voriconazole administered.