Oral absorption of voriconazole is affected by SLCO2B1 c.*396T>C genetic polymorphism in CYP2C19 poor metabolizers

Sang Won Lee, Jaeseong Oh, Andrew Hyoung Jin Kim, Sang Chun Ji, Sang In Park, Seo Hyun Yoon, Jae Young Chung, Kyung Sang Yu, In Jin Jang, Seung Hwan Lee

Research output: Contribution to journalArticle

Abstract

High pharmacokinetic variability of voriconazole is mainly explained by CYP2C19 phenotype, but there are still unknown factors affecting the variability. In this study, the effect of solute carrier organic anion transporter family member 2B1 (SLCO2B1) genotype on the pharmacokinetics (PKs) of voriconazole was evaluated in 12 healthy CYP2C19 poor metabolizers after a single administration of voriconazole 200 mg intravenously and orally. In addition, the influence of CYP3A4 enzyme activity was also explored. The oral absorption of voriconazole was decreased and delayed in the subjects with the SLCO2B1 c.*396T>C variant compared to the subjects with wild type. However, the CYP3A activity markers measured in this study did not show significant association with metabolism of voriconazole. The results suggest that the SLCO2B1 c.*396T>C may be associated with the decreased function of intestinal OATP2B1, and it could contribute to interindividual PK variability of voriconazole.

Original languageEnglish
JournalPharmacogenomics Journal
DOIs
StatePublished - 2020

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