Correlation of cyp2c19 phenotype with voriconazole plasma concentration in children

Atsushi Narita, Hideki Muramatsu, Hirotoshi Sakaguchi, Sayoko Doisaki, Makito Tanaka, Asahito Hama, Akira Shimada, Yoshiyuki Takahashi, Nao Yoshida, Kimikazu Matsumoto, Koji Kato, Kazuko Kudo, Yoko Furukawa-Hibi, Kiyofumi Yamada, Seiji Kojima

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Voriconazole is a triazole antifungal agent with potent activity against a broad spectrum of pathogens, including Aspergillus and Candida species. In human adults, allelic polymorphisms of CYP2C19 are known to correlate with significant variation in voriconazole plasma concentration. Here, we report an analysis of CYP2C19 phenotype and voriconazole plasma concentrations in children. Methods: This retrospective study included 37 children who had voriconazole plasma concentrations measured from May 2006 to June 2011. All had single-nucleotide polymorphisms that define the 3 major CYP2C19 alleles. Patients were classified as follows: normal metabolizers, intermediate metabolizers, poor metabolizers, or hypermetabolizers. Results: The frequencies of the 3 CYP2C19 genetic polymorphisms were similar to those previously reported for Japanese adults. Trough plasma concentrations of voriconazole were significantly higher in the poor metabolizer and intermediate metabolizer groups compared with the normal metabolizer and hypermetabolizer groups (P=0.004). Two patients with high plasma concentrations experienced voriconazole-related severe adverse events (syndrome of inappropriate antidiuretic hormone secretion and cardiac toxicities). Conclusions: The current study suggests that a significant association exists in children between the voriconazole plasma concentration and the CYP2C19 phenotype. Dose adjustment based on CYP2C19 phenotype may be useful during voriconazole therapy, especially for Japanese children, who as a group have a higher incidence of the poor metabolizer and intermediate metabolizer phenotypes.

Original languageEnglish
JournalJournal of Pediatric Hematology/Oncology
Volume35
Issue number5
DOIs
Publication statusPublished - Jul 2013
Externally publishedYes

Fingerprint

Phenotype
Inappropriate ADH Syndrome
Triazoles
Voriconazole
Antifungal Agents
Genetic Polymorphisms
Aspergillus
Candida
Single Nucleotide Polymorphism
Cytochrome P-450 CYP2C19
Retrospective Studies
Alleles
Incidence

Keywords

  • CYP2C19
  • Drug monitoring
  • Fungal infection
  • Voriconazole

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Oncology
  • Hematology

Cite this

Correlation of cyp2c19 phenotype with voriconazole plasma concentration in children. / Narita, Atsushi; Muramatsu, Hideki; Sakaguchi, Hirotoshi; Doisaki, Sayoko; Tanaka, Makito; Hama, Asahito; Shimada, Akira; Takahashi, Yoshiyuki; Yoshida, Nao; Matsumoto, Kimikazu; Kato, Koji; Kudo, Kazuko; Furukawa-Hibi, Yoko; Yamada, Kiyofumi; Kojima, Seiji.

In: Journal of Pediatric Hematology/Oncology, Vol. 35, No. 5, 07.2013.

Research output: Contribution to journalArticle

Narita, A, Muramatsu, H, Sakaguchi, H, Doisaki, S, Tanaka, M, Hama, A, Shimada, A, Takahashi, Y, Yoshida, N, Matsumoto, K, Kato, K, Kudo, K, Furukawa-Hibi, Y, Yamada, K & Kojima, S 2013, 'Correlation of cyp2c19 phenotype with voriconazole plasma concentration in children', Journal of Pediatric Hematology/Oncology, vol. 35, no. 5. https://doi.org/10.1097/MPH.0b013e3182880eaa
Narita, Atsushi ; Muramatsu, Hideki ; Sakaguchi, Hirotoshi ; Doisaki, Sayoko ; Tanaka, Makito ; Hama, Asahito ; Shimada, Akira ; Takahashi, Yoshiyuki ; Yoshida, Nao ; Matsumoto, Kimikazu ; Kato, Koji ; Kudo, Kazuko ; Furukawa-Hibi, Yoko ; Yamada, Kiyofumi ; Kojima, Seiji. / Correlation of cyp2c19 phenotype with voriconazole plasma concentration in children. In: Journal of Pediatric Hematology/Oncology. 2013 ; Vol. 35, No. 5.
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