Why Dried Blood Spots Are an Ideal Tool for CYP1A2 Phenotyping

Kesel, Pieter M. M. De; Lambert, Willy E.; Stove, Christophe

doi:10.1007/s40262-014-0150-5

Cited by 16 publications

(22 citation statements)

References 34 publications

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“…Linear calibration curves for caffeine and paraxanthine ranged from 20 to 500 pg/mg, with 20 pg/mg being the lower limit of quantification (LLOQ) for both compounds. Intra-and interbatch precision was below 12% (% relative standard deviation, %RSD) and accuracy below 7% (%bias) for all QCs (20,60,200 and 400 pg/mg).…”

Section: Hair Sample Collection Pretreatment and Analysismentioning

confidence: 89%

“…For 4 volunteers, a segmental analysis of 6 consecutive 3-cm hair segments was performed as well. At the day of hair sampling, a standard CYP1A2 phenotyping procedure was conducted in the same study population, as described elsewhere [20]. Briefly, caffeine and paraxanthine concentrations were determined with a validated method in plasma samples from volunteers that had taken a 150 mg caffeine capsule 6 hours (± 5 minutes) before sample collection [20,22].…”

Section: Cyp1a2 Phenotyping Studymentioning

confidence: 99%

“…At the day of hair sampling, a standard CYP1A2 phenotyping procedure was conducted in the same study population, as described elsewhere [20]. Briefly, caffeine and paraxanthine concentrations were determined with a validated method in plasma samples from volunteers that had taken a 150 mg caffeine capsule 6 hours (± 5 minutes) before sample collection [20,22]. By means of a written questionnaire, data on sex, age, general health status, smoking habits, caffeine intake, alcohol consumption, intake of drugs (including hormonal contraception) and cosmetic hair colouring were obtained.…”

Section: Cyp1a2 Phenotyping Studymentioning

confidence: 99%

“…In typical phenotyping approaches the paraxanthine/caffeine concentration ratio is determined 4-6 h post-administration in serum or plasma samples [19], although dried blood spots [20] and saliva [21] have proven to be appropriate matrices for this purpose as well. A CYP1A2 phenotyping procedure based on hair analysis would eliminate the need to administer a caffeine test dose, since it is expected that caffeine and paraxanthine will readily be detected in hair samples of a large part of the population given the widespread consumption of caffeine-containing beverages (e.g.…”

Section: Introductionmentioning

confidence: 99%

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

2015

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To refer to or to cite this work, please use the citation to the published version:De Kesel P., Lambert W. , Stove C. (2015). Paraxanthine/caffeine concentration ratios in hair: an alternative for plasma-based phenotyping of cytochrome P450 1A2? Clinical Pharmacokinetics, 54, 771-781. DOI 10.1007/s40262-015-0237-7 Paraxanthine/caffeine concentration ratios in hair: an alternative for plasma-based phenotyping of Abstract Background and ObjectiveAlthough 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 evaluate 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 time point 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. MethodsCaffeine 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. ResultsParaxanthine/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. ConclusionThe variability between hair and plasma ratios complicates the interpretation of hair ratios on an individual basis and, therefore, compromises their practical usefulness as alternative CYP1A2 phenotyping metrics. Key Points For the first time, the usefulness of paraxanthine/caffeine molar concentrations ratios in hair for CYP1A2 phenotyping was evaluated by comparing hair ratios from 60 healthy volunteers with reference, plasma-based CYP1A2 phenotyping indices . Although ratios in hair and plasma showed a statistically significant correlation, large deviations were found in individual cases. Investigating the influence of several factors did not provide a clear explanation for the observed deviations, complicating the interpretation of hair ratios on an individual basis.

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Section: Hair Sample Collection Pretreatment and Analysismentioning

confidence: 89%

Section: Cyp1a2 Phenotyping Studymentioning

confidence: 99%

Section: Cyp1a2 Phenotyping Studymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2015

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“…As a consequence, Bland-Altman and Passing-Bablok plots showed that paraxanthine/caffeine ratios, i.e. the CYP1A2 phenotyping metric, were highly comparable in all matrices [41].…”

Section: Dried Blood Spotsmentioning

confidence: 92%

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

2015

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Interindividual variability in the expression and function of drug metabolizing cytochrome P (CYP) 450 enzymes, determined by a combination of genetic, non-genetic and environmental parameters, is a major source of variable drug response. Phenotyping by administration of a selective enzyme substrate, followed by the determination of a specific phenotyping metric, is an appropriate approach to assess the in vivo activity of CYP450 enzymes, as it takes into account all influencing factors. A phenotyping protocol should be as simple and convenient as possible. Typically, phenotyping metrics are determined in traditional matrices, such as blood, plasma or urine. Several sampling strategies have been proposed as an alternative for these traditional sampling techniques.In this review, we provide a comprehensive overview of available methods using dried blood spots, hair, oral fluid, exhaled breath and sweat for in vivo CYP450 phenotyping. We discuss the relation between phenotyping metrics measured in these samples and those in conventional matrices, along with the advantages and limitations of the alternative sampling techniques. Reliable phenotyping procedures for several clinically relevant CYP450 enzymes, including CYP1A2, CYP2C19 and CYP2D6, are currently available for oral fluid, breath or dried blood spots, while additional studies are needed for other CYP450 isoforms, such as CYP3A4. The role of hair analysis for this purpose remains to be established. Being non-or minimally invasive, these sampling strategies provide convenient and patient-friendly alternatives for classical phenotyping procedures, which may contribute to the implementation of CYP450 phenotyping in clinical practice. 4 Key Points Phenotyping by administration of a selective probe drug, followed by determination of a specific phenotyping metric, allows to assess the in vivo enzyme activity of CYP450 enzymes, taking into account genetic, non-genetic and environmental influencing factors. In addition to classical sampling techniques, such as blood or urine collection, reliable phenotyping procedures for several clinically relevant CYP450 enzymes are currently available for oral fluid, breath and dried blood spots.

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