• Hui-Yan Shi, Jin Yan, Wen-Hui Zhu, Guo-Ping Yang, Zhi-Rong Tan, Wei-Hua Wu, Gan Zhou, Xiao-Ping Chen, and Dong-Sheng Ouyang.
• Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, 110# Xiangya Road, Changsha, Hunan, 410078, China.
• Eur. J. Clin. Pharmacol. 2010 Nov 1; 66 (11): 1131-6.

PurposeTo assess the impacts of erythromycin on the pharmacokinetics of voriconazole and its association with CYP2C19 genotypes in healthy Chinese male subjects.MethodsA single-center, open, crossover clinical study with two treatment phases was carried out. Eighteen healthy male volunteers, including 6 CYP2C19 homozygous extensive metabolizers (EMs, *1/*1), 6 heterozygous EMs (HEMs, *1/*2 or *1/*3), and 6 CYP2C19 poor metabolizers (PMs, *2/*2 or *2/*3), were enrolled in this study. A single oral dose of 200 mg voriconazole was administrated to all subjects after 3-day pretreatment with either 500 mg erythromycin or placebo three times daily. Periods were separated by a washout period of 14 days. Serial venous blood samples were collected, and plasma concentrations of voriconazole were determined by HPLC.ResultsC(max), AUC(0-24), and AUC(0-infinity) of voriconazole were increased significantly, while oral clearance of voriconazole was decreased significantly by erythromycin administration (p < 0.001, respectively). Compared with individuals with CYP2C19 PM genotypes, individuals with CYP2C19 EM and HEM genotypes showed significantly decreased T(½), AUC(0-24), AUC(0-infinity), and increased oral clearance of voriconazole (p < 0.05, respectively). In addition, significant increases in AUC(0-24) and AUC(0-infinity) and decreases in oral clearance of voriconazole after erythromycin treatment were observed in CYP2C19 HEMs and PMs (p < 0.05, respectively), but not in CYP2C19 EMs.ConclusionBoth CYP2C19 genotypes and CYP3A4 inhibitor erythromycin can influence the plasma concentration of voriconazole, and erythromycin increases plasma concentration of voriconazole in a CYP2C19 genotype-dependent manner.

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