Effect of CYP2C19 polymorphism on the pharmacokinetics of voriconazole after single and multiple doses in healthy volunteers

Seung Hwan Lee, Bo Hyung Kim, Won Seok Nam, Seo Hyun Yoon, Joo-Youn Cho, Sang Goo Shin, In-Jin Jang, Kyung-Sang Yu

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

The current study assessed the influence of the CYP2C19 genotype on the pharmacokinetics and tolerability of voriconazole after single and multiple oral doses in healthy volunteers. Six subjects for the CYP2C19 homozygous extensive metabolizer (EMs), 6 for heterozygous extensive metabolizer (HEMs), and 6 for poor metabolizer (PMs) were enrolled, and their CYP2C9, CYP3A5, and MDR1 genotypes were analyzed. After a single intravenous infusion or single and multiple oral doses of 200 mg of voriconazole, plasma concentrations of voriconazole were measured. Bioavailability was not significantly different among the CYP2C19 genotypes. Voriconazole exposure in PMs was approximately 3 times higher compared with EMs after a single intravenous or oral dose. At steady state, the plasma concentration just before the next dosing and area under the concentration-time curve from dosing to the time point of the next dosing for PMs were about 5 times and 3 times higher than EMs, respectively. These results suggest that the CYP2C19 genotype is the major determinant of the wide PK variability of voriconazole.

Original languageEnglish
Pages (from-to)195-203
Number of pages9
JournalJournal of Clinical Pharmacology
Volume52
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • CYP2C19
  • Voriconazole
  • pharmacogenomics
  • pharmacokinetics

Cite this