title: Development of cocaine-induced interstitial lung damage in two CYP2C and VKORC1 variant allele carriers.
abstract: BACKGROUND
  Often, the connection between drug use and the development of related inflammatory damage or idiosyncratic toxicities is hard to recognize and objectify. The presence of cytochrome P450 (CYP) variant genotypes appears to be a substantial susceptibility risk factor in the development of drug-induced pulmonary adverse events. We hypothesized that the presence of variant alleles may be associated with serious complications of illicit drug use.
  
  
  METHODS
  We report the cases of two cocaine users who developed a 'flu-like' syndrome with diffuse interstitial infiltrates after cocaine abuse. Genotyping for CYP (CYP2C9, CYP2C19) and vitamin K epoxide reductase complex 1 (VKORC1) allelic variants (-1639G/A and 1173C/T) was performed in these two patients. Both cases were heterozygous for VKORC1 variant alleles, and both possessed a CYP2C polymorphism (case 1: CYP2C19*1/*2; case 2: CYP2C9*1/*3).
  
  
  CONCLUSIONS
  The described drug abuse cases suggest that an association between the presence of CYP2C and VKORC1 allelic variants and cocaine-induced interstitial lung damage is highly likely. It is assumed that these polymorphisms contribute to intra-individual variability in drug response and toxicity, including cocaine response and toxicity. Moreover, the importance of including pharmacogenomics in the work-up of patients with suspected drug-induced (lung) toxicity, such as alveolar hemorrhage, is highlighted by these cases.
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Petal A H M
authors.initials: PA
authors.lastname: Wijnen
authors.forename: Otto
authors.initials: O
authors.lastname: Bekers
authors.forename: Marjolein
authors.initials: M
authors.lastname: Drent
mesh_terms: D000328:Adult; D003042:Cocaine / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D011859:Radiography; D064417:Vitamin K Epoxide Reductases; D055815:Young Adult
chemical_list: C400322:cytochrome P-450 CYP2C subfamily; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D003042:Cocaine