title: Correlation of CYP2C19 genotype with plasma voriconazole levels: a preliminary retrospective study in Indians.
abstract: BACKGROUND
  Voriconazole is an antifungal drug essentially metabolized by cytochrome P450 (CYP2C19) isozyme. Plasma voriconazole levels exhibit wide inter-individual variability due to several factors like age, weight, food or drug interactions or CYP2C19 polymorphisms.
  
  
  OBJECTIVE
  In the present study, we assessed the correlation of voriconazole levels with CYP2C19 genotype in patients on voriconazole therapy.
  
  
  METHODS
  Biochemistry Department of a 480 inpatient bed tertiary care hospital in India.
  
  
  METHODS
  Plasma voriconazole estimation was done in seventy-two patients on standard weight based voriconazole therapy by High Performance Liquid Chromatography (HPLC) while genotype assessment for the CYP2C19*2 and *3 was done by PCR-RFLP and *17 by ARMS-PCR. Statistical analysis and genotype-phenotype correlation was done by comparing the drug levels with the CYP2C19 genotype.
  
  
  METHODS
  CYP2C19 polymorphisms influence voriconazole metabolism.
  
  
  RESULTS
  A wide variability is seen in plasma levels with only 51% attaining therapeutic levels. The allele frequency of *2, *3 and *17 variant were found to be 33.3, 0.7 and 18% respectively. The drug levels in carriers of *2 allele (poor metabolizers) was twofold higher than that in extensive metabolizers. However, the influence of *2 allele was compromised in presence of *17 allele and patients had low voriconazole levels. In addition to the genotype, co-medication and clinical condition remarkably influenced voriconazole concentration.
  
  
  CONCLUSIONS
  Plasma voriconazole levels are influenced by CYP2C19 variants, drug interactions and clinical condition of the patient. Genotype assessment at initiation of therapy followed by drug monitoring would help optimizing therapeutic efficacy and minimizing toxicity.
authors.affiliation: Research Laboratories, P.D. Hinduja Hospital and Medical Research Centre, V.S. Marg, Mahim, Mumbai, 400016, India.
authors.forename: Prerna K
authors.initials: PK
authors.lastname: Chawla
authors.affiliation: Department of Laboratory Medicine, P.D. Hinduja Hospital & Medical Research Centre, V.S. Marg, Mahim, Mumbai, 400016, India.
authors.forename: Shweta R
authors.initials: SR
authors.lastname: Nanday
authors.affiliation: Research Laboratories, P.D. Hinduja Hospital and Medical Research Centre, V.S. Marg, Mahim, Mumbai, 400016, India.|Department of Laboratory Medicine, P.D. Hinduja Hospital & Medical Research Centre, V.S. Marg, Mahim, Mumbai, 400016, India.
authors.forename: Alpa J
authors.initials: AJ
authors.lastname: Dherai
authors.affiliation: Department of Internal Medicine, P.D. Hinduja Hospital & Medical Research Centre, V.S. Marg, Mahim, Mumbai, 400016, India.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Soman
authors.affiliation: Department of Laboratory Medicine, P.D. Hinduja Hospital & Medical Research Centre, V.S. Marg, Mahim, Mumbai, 400016, India.
authors.forename: Rohan V
authors.initials: RV
authors.lastname: Lokhande
authors.affiliation: Department of Laboratory Medicine, P.D. Hinduja Hospital & Medical Research Centre, V.S. Marg, Mahim, Mumbai, 400016, India.
authors.forename: Prasad R
authors.initials: PR
authors.lastname: Naik
authors.affiliation: Research Laboratories, P.D. Hinduja Hospital and Medical Research Centre, V.S. Marg, Mahim, Mumbai, 400016, India. dr_tashavaid@hindujahospital.com.|Department of Laboratory Medicine, P.D. Hinduja Hospital & Medical Research Centre, V.S. Marg, Mahim, Mumbai, 400016, India. dr_tashavaid@hindujahospital.com.
authors.forename: Tester F
authors.initials: TF
authors.lastname: Ashavaid
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000935:Antifungal Agents / Q000097:blood* / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D012189:Retrospective Studies; D065819:Voriconazole / Q000097:blood* / Q000493:pharmacokinetics*; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D065731:Cytochrome P-450 CYP2C19; D065819:Voriconazole
keywords: CYP2C19; Genotype-phenotype correlation; India; Therapeutic drug monitoring; Voriconazole