A Personalized CYP2C19 Phenotype-Guided Dosing Regimen of Voriconazole Using a Population Pharmacokinetic Analysis
AbstractHighly variable and non-linear pharmacokinetics of voriconazole are mainly caused by CYP2C19 polymorphisms. This study aimed to develop a mechanistic population pharmacokinetic model including the CYP2C19 phenotype, and to assess the appropriateness of various dosing regimens based on the therapeutic target. A total of 1,828 concentrations from 193 subjects were included in the population pharmacokinetic analysis. A three-compartment model with an inhibition compartment appropriately described the voriconazole pharmacokinetics reflecting auto-inhibition. Voriconazole clearance in the CYP2C19 intermediate metabolizers (IMs) and poor metabolizers (PMs) decreased by 17% and 53% compared to that in the extensive metabolizers (EMs). There was a time-dependent inhibition of clearance to 16.2% of its original value in the CYP2C19 EMs, and the extent of inhibition differed according to the CYP2C19 phenotypes. The proposed CYP2C19 phenotype-guided initial dosing regimens are 400 mg twice daily (bid) for EMs, 200 mg bid for IMs, and 100 mg bid for PMs. This CYP2C19 phenotype-guided initial dosing regimen will provide a rationale for individualizing the optimal voriconazole therapy. View Full-Text
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Kim, Y.; Rhee, S.-J.; Park, W.B.; Yu, K.-S.; Jang, I.-J.; Lee, S. A Personalized CYP2C19 Phenotype-Guided Dosing Regimen of Voriconazole Using a Population Pharmacokinetic Analysis. J. Clin. Med. 2019, 8, 227.
Kim Y, Rhee S-J, Park WB, Yu K-S, Jang I-J, Lee S. A Personalized CYP2C19 Phenotype-Guided Dosing Regimen of Voriconazole Using a Population Pharmacokinetic Analysis. Journal of Clinical Medicine. 2019; 8(2):227.Chicago/Turabian Style
Kim, Yun; Rhee, Su-jin; Park, Wan B.; Yu, Kyung-Sang; Jang, In-Jin; Lee, SeungHwan. 2019. "A Personalized CYP2C19 Phenotype-Guided Dosing Regimen of Voriconazole Using a Population Pharmacokinetic Analysis." J. Clin. Med. 8, no. 2: 227.
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