Related Experiment Video
Updated: Nov 30, 2025
Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
Predictors of Adverse Events and Determinants of the Voriconazole Trough Concentration in Kidney Transplantation
Yi-Chang Zhao1,2, Xiao-Bin Lin3, Bi-Kui Zhang1,2
1Department of Clinical Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China.
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 R2 = 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.
Insights
Predicting adverse events in kidney transplant patients treated with voriconazole is possible. Key factors include voriconazole levels, cytochrome P450 2C19 (CYP2C19) genetics, and hemoglobin levels.
Area of Science:
- Pharmacogenomics and Transplant Medicine
Background:
- Voriconazole is crucial for invasive fungal infections post-kidney transplant.
- Its metabolism is influenced by CYP2C19 variants, liver function, and other drugs.
- Voriconazole use is linked to significant adverse events.
Purpose of the Study:
- To identify predictors of voriconazole-related adverse events in kidney transplant recipients.
- To quantify the relationship between patient factors and voriconazole trough concentrations.
Main Methods:
- Prospective analysis of 93 kidney transplant recipients.
- Binary logistic regression to identify adverse event predictors.
- Multiple linear modeling to assess trough concentration determinants.
- Recorded 213 voriconazole trough concentrations.
Main Results:
- Voriconazole trough concentration (OR 2.614), CYP2C19 genotype, and hemoglobin (OR 0.181) predicted adverse events with 91.30% accuracy.
- CYP2C19 phenotypes, hemoglobin, platelet count, and ilaprazole use correlated with voriconazole levels (R² = 0.336).
Conclusions:
- CYP2C19 genotype, hemoglobin, and voriconazole trough concentration are key predictors of adverse events.
- CYP2C19 phenotype, hemoglobin, platelet count, and ilaprazole use influence voriconazole levels.
- Considering these factors can optimize voriconazole therapy and minimize risks.
Related Concept Videos
01:29Therapeutic Drug Monitoring: Affecting Factors
01:28Kidney Transplant I: Introduction
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:25Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant
01:17Factors Affecting Renal Clearance: Renal Impairment
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
01:31Factors Affecting Renal Clearance: Drug's Physicochemical Properties and Plasma Levels
One important factor is the drug's molecular size. The kidneys readily excrete smaller molecules below 300 Daltons (Da). On the other hand, molecules weighing between 300 and 500 Da are excreted through both urine and bile. Larger molecules above 500 Da tend to be excreted...