title: Inter-individual Variability of Coumarin 7-hydroxylation (CYP2A6 activity) in an Iranian Population.
abstract: OBJECTIVE
  Coumarin hydroxylase (CYP2A6) is a polymorphic enzyme, and during the last decade has received a lot of attention because it is the principle human nicotine C-oxidase, which activates a number of procarcinogens, and metabolizes drugs.
  
  
  METHODS
  150 healthy Iranian volunteers, (96 male, 54 female) aged 19 to 63 years old, were given 5 mg coumarin orally after an overnight fast. Urine samples were collected before drug administration and 2, 4 and 8 h after that. The extent and rate of the formation of 7-OH-coumarin (7OHC) was determined by the urinary excretion of the metabolite as measured by the fluorometric method.
  
  
  RESULTS
  The proportion of 7OHC excreted during the first 2 hr compared to the 7OHC excretion at 8 h was the constant and stable individual characteristic for the rate of the formation of 7OHC (2 hr coumarin test). The total amount of 7OHC formed was 32.7±12.4% (mean±SD) of the given dose. On average, 66.0% of 7OHC formed was excreted in 2 hr. No clear-cut polymorphism in the rate of 7OHC formation was found. The total amounts of 7OHC excreted were significantly lower in females. Also, the rate and amount of coumarin metabolism in Iranian population were lower than Turkish and Finnish populations.
  
  
  CONCLUSIONS
  Because of the importance of enzyme activity in drug metabolism, caution should be exercised in prescribing compounds metabolized by CYP2A6 enzyme in Iranian population.
authors.affiliation: Drug research center, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, 91775-1365, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hassanzadeh Khayyat
authors.forename: Nasser
authors.initials: N
authors.lastname: Vahdati Mashhadian
authors.forename: Saeed
authors.initials: S
authors.lastname: Eghbal
authors.forename: Navid
authors.initials: N
authors.lastname: Jalali
keywords: 7-hydroxycoumarin; CYP2A6; Coumarin; Fluorometry; Iran; Polymorphism