title: Paraxanthine/Caffeine Concentration Ratios in Hair: An Alternative for Plasma-Based Phenotyping of Cytochrome P450 1A2?
abstract: OBJECTIVE
  Although metabolite-to-parent drug concentration ratios in hair have been suggested as a possible tool to study the metabolism of drugs in a non-invasive way, no studies are available that evaluated this in a systematic way. Cytochrome P450 (CYP) 1A2 is a drug-metabolizing enzyme characterized by large inter-individual differences in its activity. The standard approach for CYP1A2 phenotyping is to determine the paraxanthine/caffeine ratio in plasma at a fixed timepoint after intake of a dose of the CYP1A2 substrate caffeine. The aim of this study was to evaluate whether paraxanthine/caffeine ratios measured in hair samples reflect the plasma-based CYP1A2 phenotype.
  
  
  METHODS
  Caffeine and paraxanthine concentrations were measured in proximal 3 cm segments of hair samples from 60 healthy volunteers and resulting paraxanthine/caffeine ratios were correlated with CYP1A2 phenotyping indices in plasma.
  
  
  RESULTS
  Paraxanthine/caffeine ratios in hair ranged from 0.12 to 0.93 (median 0.41); corresponding ratios in plasma ranged from 0.09 to 0.95 (median 0.40). A statistically significant correlation was found between ratios in hair and plasma (r = 0.41, p = 0.0011). However, large deviations between ratios in both matrices were found in individual cases. Although the influence of several factors on paraxanthine/caffeine ratios and hair-plasma deviations was investigated, no evident factors explaining the observed variability could be identified.
  
  
  CONCLUSIONS
  The variability between hair and plasma ratios complicates the interpretation of hair paraxanthine/caffeine ratios on an individual basis and, therefore, compromises their practical usefulness as alternative CYP1A2 phenotyping matrix.
authors.affiliation: Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
authors.forename: Pieter M M
authors.initials: PM
authors.lastname: De Kesel
authors.forename: Willy E
authors.initials: WE
authors.lastname: Lambert
authors.forename: Christophe P
authors.initials: CP
authors.lastname: Stove
mesh_terms: D000328:Adult; D002110:Caffeine / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D019388:Cytochrome P-450 CYP1A2 / Q000097:blood / Q000378:metabolism*; D005260:Female; D006197:Hair / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013806:Theophylline / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D002110:Caffeine; D013806:Theophylline; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; C021183:1,7-dimethylxanthine