title: A prospective observational study of CYP2C19 polymorphisms and voriconazole plasma level in adult Thai patients with invasive aspergillosis.
abstract: 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 μg/ml) was statistically significantly higher than those with the 636GG genotype (1.596, IQR 0.755-2.980 μg/ml), P = 0.046. The patients with a poor metabolizer (PM; CYP2C19*2/*2, *2/*3) had voriconazole Ctrough level of 1.900 (IQR, 1.130-3.673 μg/ml). This was statistically significantly higher than that seen with the extensive metabolizer phenotype (1.470; IQR, 0.632-2.720 μg/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.
authors: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors: Sumonrat
authors: S
authors: Chuwongwattana
authors: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors: Thawinee
authors: T
authors: Jantararoungtong
authors: Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors: Maria N
authors: MN
authors: Chitasombat
authors: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors: Apichaya
authors: A
authors: Puangpetch
authors: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors: Santirat
authors: S
authors: Prommas
authors: Department of Clinical Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
authors: Pitchaya
authors: P
authors: Dilokpattanamongkol
authors: Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors: Siriorn P
authors: SP
authors: Watcharananan
authors: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand. Electronic address: chonlaphat.suk@mahidol.ac.th.
authors: Chonlaphat
authors: C
authors: Sukasem
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001228:Aspergillosis / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D013785:Thailand; D065819:Voriconazole / Q000097:blood* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D065731:Cytochrome P-450 CYP2C19; D065819:Voriconazole
keywords: CYP2C19 polymorphism; Plasma level; SNP; Thai; Voriconazole