A prospective observational study of CYP2C19 polymorphisms and voriconazole plasma level in adult Thai patients with invasive aspergillosis

作者：Chuwongwattana Sumonrat; Jantararoungtong Thawinee; Chitasombat Maria N; Puangpetch Apichaya; Prommas Santirat; Dilokpattanamongkol Pitchaya; Watcharananan Siriorn P; Sukasem Chonlaphat^*

来源：Drug Metabolism and Pharmacokinetics, 2016, 31(2): 117-122.

DOI：10.1016/j.dmpk.2015.12.005

• Voriconazole
• CYP2C19 polymorphism
• Thai
• Plasma level
• SNP

The aim of this study was to investigate the association of genetic variants of CYP2C19 (CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles) and voriconazole trough plasma concentrations in Thai patients with invasive fungal infection. A total of 285 samples from patients with invasive fungal infection and treated with voriconazole were prospectively enrolled. At steady state, trough voriconazole concentrations were measured using tandem mass spectrophotometry and high performance liquid chromatography. The genetic variants in the CYP2C19 gene were genotyped for CYP2C19*2 (G681A), CYP2C19*3 (G636A) and CYP2C19*17 (C-806T) on plasma voriconazole level. Voriconazole Ctrough levels were positively associated with CYP2C19*3. The median Ctrough level for patients with the 636GA genotype (2.109, IQR 1.054 -4.166 mu g/ml) was statistically significantly higher than those with the 636GG genotype (1.596, IQR 0.755 -2.980 mu g/ml), P = 0.046. The patients with a poor metabolizer (PM; CYP2C19*22, *23) had voriconazole Ctrough level of 1.900 (IQR, 1.130-3.673 mg/ml). This was statistically significantly higher than that seen with the extensive metabolizer phenotype (1.470; IQR, 0.632-2.720 mu g/ml), P = 0.039. An association between CYP2C19 variant alleles and high voriconazole plasma level was identified. Therefore, determining the CYP2C19 genotype before initiation of voriconazole treatment may be useful in optimizing the dosing regimen in Thai patients with invasive fungal infections.

• 出版日期2016-4