Paraxanthine/caffeine concentration ratios in hair: an alternative for plasma-based phenotyping of cytochrome P450 1A2?
| Autor: | Christophe P. Stove, Willy E. Lambert, Pieter M. M. De Kesel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Saliva Pharmacology toxicology CAFFEINE TEST CYP1A2 ACTIVITY Pharmacology METABOLISM SALIVA chemistry.chemical_compound Young Adult Theophylline Cytochrome P-450 CYP1A2 Caffeine Healthy volunteers Humans Pharmacology (medical) DRUG PROBE Paraxanthine biology Chemistry CYP1A2 Cytochrome P450 Middle Aged Drug concentration Phenotype biology.protein Female PREGNANT-WOMEN Hair HEALTHY-VOLUNTEERS |
| Zdroj: | CLINICAL PHARMACOKINETICS |
| ISSN: | 0312-5963 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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