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Paraxanthine/Caffeine Concentration Ratios in Hair: An Alternative for Plasma-Based Phenotyping of Cytochrome P450 1A2?

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Abstract

Background and 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.

Conclusion

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.

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Acknowledgments

The authors wish to thank all volunteers who participated in the phenotyping study.

Conflict of interest

The authors have no conflicts of interest to declare. This study was financed by the Laboratory of Toxicology, Ghent University, Ghent, Belgium. The authors received no additional funding directly related to the content of this study.

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Authors and Affiliations

  1. Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium

    Pieter M. M. De Kesel, Willy E. Lambert & Christophe P. Stove

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  1. Pieter M. M. De Kesel
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  2. Willy E. Lambert
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  3. Christophe P. Stove
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Correspondence to Christophe P. Stove.

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De Kesel, P.M.M., Lambert, W.E. & Stove, C.P. Paraxanthine/Caffeine Concentration Ratios in Hair: An Alternative for Plasma-Based Phenotyping of Cytochrome P450 1A2?. Clin Pharmacokinet 54, 771–781 (2015). https://doi.org/10.1007/s40262-015-0237-7

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