Correlation between plasma concentration of voriconazole and polymorphisms in CYP2C19, CYP2C9 and CYP3A5 genes in children
10.12206/j.issn.2097-2024.202402020
- VernacularTitle:儿童伏立康唑的血药浓度与CYP2C19、CYP2C9和CYP3A5基因多态性的相关性研究
- Author:
Mingzhu GUI
1
;
Jing LI
1
;
Zhiling LI
2
Author Information
1. Department of Pediatrics, Luodian Hospital of Baoshan District, Shanghai 201908, China.
2. Department of Pharmacy, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China.
- Publication Type:Originalarticles
- Keywords:
voriconazole;
pharmacogenes;
blood drug concentrations;
pediatric
- From:
Journal of Pharmaceutical Practice and Service
2026;44(2):76-79
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of CYP2C19, CYP2C9 and CYP3A5 genotypes on the plasma concentration of voriconazole in children. Methods Collected blood samples from 50 hospitalized children with invasive fungal infections who received intravenous voriconazole from January 2020 to December 2020. High performance liquid chromatography was used to detect the blood trough concentration of voriconazole, and the time-of-flight mass spectrometry detection system was used to detect the genotypes of CYP2C19, CYP2C9 and CYP3A5, and the effects of children’s genotyping on the plasma concentration, efficacy and adverse reactions of voriconazole were analyzed. Results The total effective rate of 50 children with IFI was 84% （42/50 cases） after voriconazole treatment. The incidence of adverse reactions was 20% （10/50 cases）. The measured plasma concentration of voriconazole ranged from 0.56~7.62 μg/ml. Combined with the different mutation types of CYP2C19 gene loci, three metabolic activities were produced: fast, medium and slow, and the test results showed that there were 16 cases of fast metabolism, 27 cases of intermediate metabolism and 7 cases of slow metabolism. There was a significant difference in plasma concentrations among the three groups （F=15.359, P<0.001）, and the drug concentrations in the fast metabolic group were significantly lower than those in the intermediate metabolic and slow metabolic groups. The mutations of CYP2C9 and CYP3A5 had no significant effect on the plasma concentrations of the drugs, which were （F=2.213, P=0.086 and F=0.757, P=0.475）. Conclusion Voriconazole had significant efficacy in the treatment of invasive fungal infections in children, and the adverse reactions were mild. CYP2C19 genotype was significantly related to the rate of drug metabolism and was an important factor affecting blood drug concentration, the detection of drug concentration and genotype of voriconazole was helpful to adjust the effective drug dose clinically and would achieve more scientific and individualized treatment.
