PMID- 36072540
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220910
IS  - 2224-4344 (Print)
IS  - 2224-4344 (Electronic)
IS  - 2224-4336 (Linking)
VI  - 11
IP  - 8
DP  - 2022 Aug
TI  - Therapeutic drug monitoring and CYP2C19 genotyping guide the application of 
      voriconazole in children.
PG  - 1311-1322
LID - 10.21037/tp-22-156 [doi]
AB  - BACKGROUND: This study used therapeutic drug monitoring (TDM) and CYP2C19 gene 
      polymorphism analysis to explore the efficacy and safety of different doses of 
      voriconazole (VCZ) for the clinical treatment of pediatric patients, with the aim 
      of providing guidelines for individualized antifungal therapy in children. 
      METHODS: Our study enrolled 94 children with 253 VCZ concentrations. The 
      genotyping of CYP2C19 was performed by polymerase chain reaction 
      (PCR)-pyrosequencing. VCZ trough concentration (C(trough)) was detected by 
      high-performance liquid chromatography-tandem mass spectrometry. SPSS 23.0 was 
      used to analyze the correlations between VCZ concentration, CYP2C19 phenotype, 
      adverse effects (AEs), and drug-drug interactions. RESULTS: A total of 94 
      children aged between 1 and 18 years (median age 6 years) were enrolled in the 
      study. In total, 42.6% of patients reached the therapeutic range at initial 
      dosing, while the remaining patients reached the therapeutic range after the 
      adjustment of the dose or dosing interval. CYP2C19 gene polymorphism was 
      performed in 59 patients. Among these patients, 24 (40.7%) had the normal 
      metabolizer (NM) phenotype, 26 (44.1%) had the intermediate metabolizer (IM) 
      phenotype, and 9 (15.3%) had the poor metabolizer (PM) phenotype. No cases of the 
      rapid metabolizer (RM) or ultrarapid metabolizer (UM) phenotypes were found. The 
      initial VCZ C(trough) was significantly higher in patients with the PM and IM 
      phenotypes than in those with the NM phenotype. The combination of 
      immunosuppressive drugs (ISDs) did not affect VCZ C(trough). The incidence of AEs 
      was 25.5%, and liver function damage (46.2%) and gastrointestinal reactions 
      (19.2%) were the most common. CONCLUSIONS: Our study showed significant 
      individual differences of VCZ metabolism in children. Combining TDM with CYP2C19 
      gene polymorphism has important guiding significance for individualized 
      antifungal therapy in pediatric patients.
CI  - 2022 Translational Pediatrics. All rights reserved.
FAU - Chen, Xiaomin
AU  - Chen X
AD  - Department of Pediatrics, Nanfang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Xiao, Yuhua
AU  - Xiao Y
AD  - Department of Pediatrics, Nanfang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Li, Huiping
AU  - Li H
AD  - Department of Pediatrics, Nanfang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Huang, Zhi
AU  - Huang Z
AD  - Department of Pediatrics, Nanfang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Gao, Jingyu
AU  - Gao J
AD  - Department of Pediatrics, Nanfang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Zhang, Xinyao
AU  - Zhang X
AD  - Department of Pediatrics, Nanfang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Li, Yirong
AU  - Li Y
AD  - Department of Pediatrics, Nanfang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Van Timothee, Bindanda Mvuama
AU  - Van Timothee BM
AD  - Department of Pediatrics, Nanfang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Feng, Xiaoqin
AU  - Feng X
AD  - Department of Pediatrics, Nanfang Hospital, Southern Medical University, 
      Guangzhou, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Transl Pediatr
JT  - Translational pediatrics
JID - 101649179
PMC - PMC9442201
OTO - NOTNLM
OT  - CYP2C19
OT  - Voriconazole (VCZ)
OT  - therapeutic drug monitoring (TDM)
OT  - therapy
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at 
      https://tp.amegroups.com/article/view/10.21037/tp-22-156/coif). The authors have 
      no conflicts of interest to declare.
EDAT- 2022/09/09 06:00
MHDA- 2022/09/09 06:01
PMCR- 2022/08/01
CRDT- 2022/09/08 02:27
PHST- 2022/03/07 00:00 [received]
PHST- 2022/07/19 00:00 [accepted]
PHST- 2022/09/08 02:27 [entrez]
PHST- 2022/09/09 06:00 [pubmed]
PHST- 2022/09/09 06:01 [medline]
PHST- 2022/08/01 00:00 [pmc-release]
AID - tp-11-08-1311 [pii]
AID - 10.21037/tp-22-156 [doi]
PST - ppublish
SO  - Transl Pediatr. 2022 Aug;11(8):1311-1322. doi: 10.21037/tp-22-156.