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

• Published in: The pharmacogenomics journal Vol. 20; no. 6; pp. 792 - 800
• Main Authors: Lee, Sang Won, Oh, Jaeseong, Kim, Andrew HyoungJin, Ji, Sang Chun, Park, Sang-In, Yoon, Seo Hyun, Chung, Jae-Young, Yu, Kyung-Sang, Jang, In-Jin, Lee, SeungHwan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2020; Nature Publishing Group
• Subjects: 45/77; 631/208/212/1728; 692/308/53/2423; Antifungal agents; Biomarkers; Biomedical and Life Sciences; Biomedicine; Drug dosages; Enzymatic activity; Enzymes; Fungal infections; Gene Expression; Gene polymorphism; Hospitals; Human Genetics; Intestine; Medicine; Metabolism; Oncology; Organic anion transporting polypeptide; Pharmacokinetics; Pharmacology; Pharmacotherapy; Phenotypes; Plasma; Polymorphism; Psychopharmacology; Quality control; Voriconazole
• ISSN: 1470-269X; 1473-1150; 1473-1150
• DOI: 10.1038/s41397-020-0166-1

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.