Evaluation of caffeine as a test drug for CYP1A2, NAT2 and CYP2E1 phenotyping in man by in vivo versus in vitro correlations

Fuhr, Uwe; Rost, Karl Ludwig; Engelhardt, R.; Sachs, Michael; Liermann, D.; Belloc, C.; Beaune, P; Janezic, Susan A.; Grant, Denis M.; Meyer, Urs; Staib, A. H.

doi:10.1097/00008571-199604000-00003

Cited by 114 publications

(104 citation statements)

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“…Furthermore, in a study involving 25 patients undergoing hepatectomy, significant correlations were found between in vivo parameters of CYP1A2 activity, being caffeine clearance and paraxanthine/caffeine ratios (3 and 6 h post-dose) in oral fluid or plasma, and in vitro parameters, being caffeine 3-demethylation and relative CYP1A2 content in liver microsomes [13]. Since then, the validity of oral fluid for CYP1A2 phenotyping was corroborated by several other studies [81][82][83][84][85][86][87] and, consequently, this approach has been widely applied to assess CYP1A2 activity in various settings [61,85,86,[88][89][90][91][92][93][94][95][96][97][98].…”

Section: Oral Fluidmentioning

confidence: 98%

“…Typically, these breath tests are based on oral or intravenous administration of an isotopically labeled test compound. While radioactive 14 C-labeled compounds were initially used, probe drugs carrying a functional group in which a stable 13 C-isotope replaces a 12 C-atom have now become standard practice, thereby providing a safer alternative. Upon administration, the probe drug is subject to metabolism and the labeled functional group is enzymatically cleaved.…”

Section: Exhaled Breathmentioning

confidence: 99%

“…Apart from their use to investigate liver function, 13 C breath tests have been applied to quantitatively assess the activity of metabolic enzymes. For many probe drugs, the initial metabolic reaction, often a dealkylation step, is catalyzed by CYP450 enzymes and, therefore, the amount of 13 CO 2 in breath should reflect enzyme activity.…”

Section: Exhaled Breathmentioning

confidence: 99%

“…[ 13 C]-pantoprazole has been proposed as an alternative CYP2C19 phenotyping probe, as several studies found significantly lower DOB values in CYP2C19 poor metabolizers compared to intermediate or extensive metabolizers [124][125][126][127][128][129]. In addition, plasma [ 13 C]-pantoprazole AUC correlated significantly with the AUC of DOB 13 [130]. The utility of this approach was evaluated by Opdam et al in a study involving breast cancer patients taking tamoxifen, a prodrug that is converted to endoxifen by CYP2D6.…”

Section: Exhaled Breathmentioning

confidence: 99%

“…Concerning urine sampling, the susceptibility to non-specific noise caused by urinary flow or pH is a matter of concern. For example, urinary metabolic ratios of the probe drugs caffeine and dextromethorphan for phenotyping of CYP1A2 and CYP2D6, respectively, showed high intraindividual variability caused by these variables [13,14]. Furthermore, phenotyping protocols often require that urine is collected over a period of several hours.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Oral Fluidmentioning

confidence: 98%

Section: Exhaled Breathmentioning

confidence: 99%

Section: Exhaled Breathmentioning

confidence: 99%

Section: Exhaled Breathmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

2015

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Validation of a high-performance liquid chromatography assay for quantification of caffeine and paraxanthine in human serum in the context of CYP1A2 phenotyping

Koch

Tusscher

Koppe

et al. 1999

Biomed. Chromatogr.

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N‐Acetyltransferase 2 (Phänotypisierung: Coffein‐Test) [Biomonitoring Methods in German language, 2004]

Blaszkewicz¹

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Analytische Methoden zur Prüfung gesundheitsschädlicher Arbeitsstoffe: Analysen in biologischem Material , 16. Lieferung, Ausgabe 2004 Der Artikel enthält folgende Kapitel: Zusammenfassung Grundlage des Verfahrens Geräte, Chemikalien und Lösungen Geräte Chemikalien Lösungen Vergleichsstandards Probenahme und Probenvorbereitung Probenahme Probenaufbereitung Instrumentelle Arbeitsbedingungen Hochleistungsflüssigchromatographische Arbeitsbedingungen Analytische Bestimmung Kalibrierung und Berechnung der Analysenergebnisse Standardisierung der Messergebnisse und Qualitätssicherung Beurteilung des Verfahrens Präzision Richtigkeit Nachweisgrenzen Störeinflüsse Diskussion der Methode Addendum

show abstract

Evaluation of caffeine as a test drug for CYP1A2, NAT2 and CYP2E1 phenotyping in man by in vivo versus in vitro correlations

Cited by 114 publications

References 0 publications

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

Validation of a high-performance liquid chromatography assay for quantification of caffeine and paraxanthine in human serum in the context of CYP1A2 phenotyping

N‐Acetyltransferase 2 (Phänotypisierung: Coffein‐Test) [Biomonitoring Methods in German language, 2004]

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