Predictors of Adverse Events and Determinants of the Voriconazole Trough Concentration in Kidney Transplantation Recipients

Abstract

Voriconazole is the mainstay for the treatment of invasive fungal infections in patients who underwent a kidney transplant. Variant CYP2C19 alleles, hepatic function, and concomitant medications are directly involved in the metabolism of voriconazole. However, the drug is also associated with numerous adverse events. The purpose of this study was to identify predictors of adverse events using binary logistic regression and to measure its trough concentration using multiple linear modeling. We conducted a prospective analysis of 93 kidney recipients cotreated with voriconazole and recorded 213 trough concentrations of it. Predictors of the adverse events were voriconazole trough concentration with the odds ratios (OR) of 2.614 (P = 0.016), cytochrome P450 2C19 (CYP2C19), and hemoglobin (OR 0.181, P = 0.005). The predictive power of these three factors was 91.30%. We also found that CYP2C19 phenotypes, hemoglobin, platelet count, and concomitant use of ilaprazole had quantitative relationships with voriconazole trough concentration. The fit coefficient of this regression equation was R 2 = 0.336, demonstrating that the model explained 33.60% of interindividual variability in the disposition of voriconazole. In conclusion, predictors of adverse events are CYP2C19 phenotypes, hemoglobin, and voriconazole trough concentration. Determinants of the voriconazole trough concentration were CYP2C19 phenotypes, platelet count, hemoglobin, concomitant use of ilaprazole. If we consider these factors during voriconazole use, we are likely to maximize the treatment effect and minimize adverse events. Invasive fungal infections are a feared complication in kidney transplant recipients, occurring in 0.1-3.5% of solid organ recipients. 1 Its 12-week survival rates were only 60.7%, and 22.1% of the survivors experienced graft loss because of invasive fungal infections. 2 Kidney transplantation, in conjunction with calcineurin inhibitors, is regarded as the best

Factors Affecting Voriconazole Trough Concentration and Optimal Maintenance Voriconazole Dose in Chinese Children

“…Therefore, the interaction between tacrolimus and voriconazole has also been widely concerned [ 5 , 6 ]. The result of our previous study in kidney transplantation recipients was that the combination use of tacrolimus was associated with voriconazole concentration; however, in further multiple linear regression analysis, tacrolimus was not identified as the final influencing factor of voriconazole concentration [ 38 ], and the results were similar to those in this study. Taken together, the drugs mentioned above may have potential drug interactions with voriconazole, but the conclusions are inconsistent; it is also necessary to pay attention to the impact of drug combination during voriconazole therapy.…”

A Large Sample Retrospective Study on the Distinction of Voriconazole Concentration in Asian Patients from Different Clinical Departments

“…The result is similar to previous findings [19,38] and conforms to the metabolic characteristics of VRZ. It has been reported that ALP had a significant effect on VRZ concentration in kidney transplantation recipients [39] and oncology patients [30]. However, there was no similar result regarding ALP in the present study.…”

Predictors of Voriconazole Trough Concentrations in Patients with Child–Pugh Class C Cirrhosis: A Prospective Study

“…The other research team members have drawn a similar conclusion for platelet count: platelet count was statistically significantly associated with voriconazole pharmacokinetics [ 35 ]. Except for the above factors, the variability of concentrations can be partly explained by non-linear kinetics, weight, liver function, concomitant medications [ 20 ], clinical and laboratory data such as C-reactive protein [ 17 , 36 ], albumin [ 37 ], and hemoglobin [ 38 ]. The different findings from these studies and the influence of sex found by this one may be due to the limited sample size and the large proportion of male patients (90.7%).…”