Evaluation of <scp>CYP1A2</scp> activity: Relationship between the endogenous urinary 6‐hydroxymelatonin to melatonin ratio and paraxanthine to caffeine ratio in dried blood spots

Magliocco, Gaëlle; Desmeules, Jules Alexandre; Samer, Caroline Flora; Thomas, Aurélien; Daali, Youssef

doi:10.1111/cts.13263

Cited by 3 publications

(1 citation statement)

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“…Very recently, Magliocco et al reported that a method for phenotyping CYP1A2 from the ratio of urinary MEL to MEL metabolites, which could not be correlated with the CYP1A2 phenotyping method of the caffeine/paraxanthine concentration ratio in DBS. 22) The reason for this may involve the influence of fluctuations in MEL renal clearance. Here, the CL m(MEL) formula can be converted as follows (X MEL : urinary MEL excretion) 8) :…”

Section: Discussionmentioning

confidence: 99%

Calculation of Human Melatonin Partial Metabolic Clearance in Healthy Adult Volunteers for Investigation of a Novel <i>in Vivo</i> CYP1A2 Phenotyping Method: A Pilot Study

Ohki

Ogawa

Takano

et al. 2023

Biological & Pharmaceutical Bulletin

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The method of administering caffeine as a probe to evaluate the phenotypic activity of the CYP1A2, has not yet been applied clinically. In contrast, if endogenous melatonin (MEL) metabolism can be used to assess CYP1A2 activity, it could be a simple method that does not require substance administration. The study aim was to calculate the MEL partial metabolic clearance (CL m(MEL) ) from plasma MEL and its urinary metabolites and to test the potential of this approach as a novel CYP1A2 phenotyping method. Nine subjects were included in the study; 3 had 6 blood and 4 urine samples collected between 10:00 and 18:00 (collectively, the intraday sample). Nine subjects had 3 blood samples and 2-h urine samples collected between 10:00 and 12:00 once a week for 3 weeks (interday sample). The CL m(MEL) was calculated from the plasma area under the curve (AUC) of MEL (AUC MEL ) and urinary MEL metabolites excretion (X 6MEL ). Among the intraday samples, the AUC MEL ranged from 6.45-13.17 pmol•h/L and X 6MEL ranged from 0.204-0.899 nmol/2 h, showing a decrease in concentration over time. In contrast, the CL m(MEL) ranged from 30.52-69.57 L/h (withinindividual percent relative standard deviation: 9.2-20.1%), showing no time-dependent variation. Large interindividual variability was observed in AUC MEL and X 6MEL in the interday sample, but CL m(MEL) showed small interindividual variabilities. The CL m(MEL) was 1.8-fold higher for smokers than for nonsmokers. The results obtained in this study may be valuable in future studies of evaluating novel CYP1A2 phenotyping method.

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Section: Discussionmentioning

confidence: 99%

Calculation of Human Melatonin Partial Metabolic Clearance in Healthy Adult Volunteers for Investigation of a Novel <i>in Vivo</i> CYP1A2 Phenotyping Method: A Pilot Study

Ohki

Ogawa

Takano

et al. 2023

Biological & Pharmaceutical Bulletin

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Evaluation of CYP1A2 activity: Relationship between the endogenous urinary 6‐hydroxymelatonin to melatonin ratio and paraxanthine to caffeine ratio in dried blood spots

Magliocco

Desmeules

Samer

et al. 2022

Clinical Translational Sci

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Circulating Biomarkers Instead of Genotyping to Establish Metabolizer Phenotypes

Tremmel,

Hofmann,

Haag

et al. 2024

Annu. Rev. Pharmacol. Toxicol.

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Pharmacogenomics (PGx) enables personalized treatment for the prediction of drug response and to avoid adverse drug reactions. Currently, PGx mainly relies on the genetic information of absorption, distribution, metabolism, and excretion (ADME) targets such as drug-metabolizing enzymes or transporters to predict differences in the patient's phenotype. However, there is evidence that the phenotype-genotype concordance is limited. Thus, we discuss different phenotyping strategies using exogenous xenobiotics (e.g., drug cocktails) or endogenous compounds for phenotype prediction. In particular, minimally invasive approaches focusing on liquid biopsies offer great potential to preemptively determine metabolic and transport capacities. Early studies indicate that ADME phenotyping using exosomes released from the liver is reliable. In addition, pharmacometric modeling and artificial intelligence improve phenotype prediction. However, further prospective studies are needed to demonstrate the clinical utility of individualized treatment based on phenotyping strategies, not only relying on genetics. The present review summarizes current knowledge and limitations. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 64 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Evaluation of CYP1A2 activity: Relationship between the endogenous urinary 6‐hydroxymelatonin to melatonin ratio and paraxanthine to caffeine ratio in dried blood spots

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 3 publications

References 51 publications

Calculation of Human Melatonin Partial Metabolic Clearance in Healthy Adult Volunteers for Investigation of a Novel <i>in Vivo</i> CYP1A2 Phenotyping Method: A Pilot Study

Calculation of Human Melatonin Partial Metabolic Clearance in Healthy Adult Volunteers for Investigation of a Novel <i>in Vivo</i> CYP1A2 Phenotyping Method: A Pilot Study

Evaluation of CYP1A2 activity: Relationship between the endogenous urinary 6‐hydroxymelatonin to melatonin ratio and paraxanthine to caffeine ratio in dried blood spots

Circulating Biomarkers Instead of Genotyping to Establish Metabolizer Phenotypes

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