title: The CYP2C19 ultra-rapid metabolizer genotype influences the pharmacokinetics of voriconazole in healthy male volunteers.
abstract: OBJECTIVE
  To study the pharmacokinetic characteristics of voriconazole in healthy Chinese male volunteers in relation to cytochrome P450 (CYP) 2C19 genotype status, including ultra-rapid metabolizers (URMs), homozygous extensive metabolizers (EMs), and poor metabolizers (PMs).
  
  
  METHODS
  Twenty healthy Chinese male volunteers were recruited for the study. Of these, four were CYP2C19 heterozygous URMs (*1/*17), eight were CYP2C19 homozygous EMs (*1/*1), and eight were CYP2C19 PMs (*2/*2). After a single oral dose of 200 mg voriconazole, plasma concentrations of voriconazole were determined for a 24-h period by liquid chromatography-mass spectrometry/mass spectrometry.
  
  
  RESULTS
  In Chinese male subjects, the allele frequencies of the CYP2C19*17 and CYP2C19*2 alleles were 0.64 and 35.6%, respectively, and both alleles were in Hardy-Weinberg equilibrium. The area under the concentration-time curve (AUC) from predose to 24 h (AUC(0-24)) and from predose to infinity (AUC(0-infinity)), and apparent oral clearance (CL/F) of voriconazole were statistically different among all three genotypic groups (P < 0.001, respectively). The maximum plasma concentration (C(max)) value of URMs also showed statistically significant differences from those of EMs and PMs (P = 0.036 and P = 0.035, respectively). The elimination half-life (t(1/2)) in URMs was 87% (P = 0.58) of that in EMs and 51% (P= 0.002) of that in PMs.
  
  
  CONCLUSIONS
  Our data indicate that the presence of the CYP2C19*17 allele results in ultra-rapid metabolism of voriconazole after a single oral dose.
authors.affiliation: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan 410078, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Wang
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Lei
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Tan
authors.forename: Dong
authors.initials: D
authors.lastname: Guo
authors.forename: Lan
authors.initials: L
authors.lastname: Fan
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.forename: Dong-Li
authors.initials: DL
authors.lastname: Hu
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
mesh_terms: D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D044466:Asian People; D002681:China; D065731:Cytochrome P-450 CYP2C19; D005838:Genotype; D006801:Humans; D008297:Male; D011743:Pyrimidines / Q000097:blood / Q000493:pharmacokinetics*; D014230:Triazoles / Q000097:blood / Q000493:pharmacokinetics*; D065819:Voriconazole; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D065819:Voriconazole