Correlation of CYP2C19 genotype with plasma voriconazole exposure in South-western Chinese Han patients with invasive fungal infections. Issue 3 (January 2019)

• Record Type: Journal Article
• Authors: Miao, Qiang; Tang, Jiang-Tao; van Gelder, Teun; Li, Ya-Mei; Bai, Yang-Juan; Zou, Yuan-Gao; Wang, Lan-Lan; Shi, Yun-Ying
• Other Names: Thachangattuthodi. Anish section editor.
• Is Part Of: Medicine. Volume 98:Issue 3(2019)
• Publication Date: 2019-01
• Subjects: CYP2C19 polymorphism -- invasive fungal infections -- therapeutic drug monitoring -- voriconazole dose-adjusted concentrations; Medicine -- Periodicals; Medicine -- Periodicals; Médecine -- Périodiques; Geneeskunde; Medicine; Periodicals; Periodicals; 610.5
• DOI: 10.1097/MD.0000000000014137
• Languages: English
• ISSNs: 0025-7974

Abstract

Abstract : Abstract: The aim of this study was to investigate the correlation between CYP2C19 genotype and dose-adjusted voriconazole (VCZ) trough concentrations (C0 /dose). We analyzed the correlation between CYP2C19 * 2 (681G>A), CYP2C19 * 3 (636G>A), and CYP2C19 * 17 (-806C>T) genetic polymorphisms and the dose-corrected pre-dose concentration (C0 /dose) in 106 South-western Chinese Han patients. The frequencies of variant alleles of CYP2C19 * 2, * 3, and * 17 were 29.7%, 4.25%, and 0.92%. For 49.3% of the VCZ samples, the therapeutic window between 1.5 and 5.5 μg/ml was reached. Following the first dose VCZ measurement, in subsequent samples the proportion of VCZ C0 within the therapeutic window increased, suggesting effective therapeutic drug monitoring (TDM) ( P = .001). The VCZ C0 was significantly different ( P = .010) between patients with normal metabolism (NMs), intermediate metabolism (IMs), and poor metabolism (PMs). The VZC C0 /dose was 12.2 (interquartile range (IQR), 8.33–18.2 μg·ml −1 /kg·day −1 ), and 7.68 (IQR, 4.07–16.3 μg·ml −1 /kg·day −1 ) in PMs and IMs patients, respectively, which was significantly higher than in NMs phenotype patients (4.68; IQR, 2.51–8.87 μg·ml −1 /kg·day −1, P = .008 and P = .014). This study demonstrated that the VCZ C0 /dose was significantly influenced by the CYP2C19 genotype in South-western Chinese Han patients. In this patient population, more over-exposure was observed in patients with a CYP2C19 genotype associated with poor or intermediate metabolism. CYP2C19 genotype-based dosing combined with TDM will support individualization of VCZ dosing, and potentially will minimize toxicity and maximize therapeutic efficacy. Abstract : Supplemental Digital Content is available in the text