Evaluation of a [13C]-dextromethorphan breath test to assess CYP2D6 phenotype.

Journal of Clinical Pharmacology
J Steven LeederDavid I Rosen

Abstract

A [(13)C]-dextromethorphan ([(13)C]-DM) breath test was evaluated to assess its feasibility as a rapid, phenotyping assay for CYP2D6 activity. [(13)C]-DM (0.5 mg/kg) was administered orally with water or potassium bicarbonate-sodium bicarbonate to 30 adult Caucasian volunteers (n=1 each): CYP2D6 poor metabolizers (2 null alleles; PM-0) and extensive metabolizers with 1 (EM-1) or 2 functional alleles (EM-2). CYP2D6 phenotype was determined by (13)CO(2) enrichment measured by infrared spectrometry (delta-over-baseline [DOB] value) in expired breath samples collected before and up to 240 minutes after [(13)C]-DM ingestion and by 4-hour urinary metabolite ratio. The PM-0 group was readily distinguishable from either EM group by both the breath test and urinary metabolite ratio. Using a single point determination of phenotype at 40 minutes and defining PMs as subjects with a DOB <or=0.5, the sensitivity of the method was 100%; specificity was 95% with 95% accuracy and resulted in the misclassification of 1 EM-1 individual as a PM. Modification of the initial protocol (timing of potassium bicarbonate-sodium bicarbonate administration relative to dose) yielded comparable results, but there was a tendency toward increased DOB values. A...Continue Reading

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Citations

May 18, 2010·European Journal of Clinical Pharmacology·Andrea GaedigkSusan Corey
Jul 23, 2013·Clinical Pharmacokinetics·Frans L OpdamHenk-Jan Guchelaar
Jan 13, 2009·The Journal of Pharmacology and Experimental Therapeutics·Zeruesenay DestaDavid A Flockhart
Dec 3, 2010·Pharmacogenomics·Mara L Becker, J Steven Leeder
Apr 1, 2011·Pharmacogenomics·Anuradha Ramamoorthy, Todd C Skaar
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Oct 25, 2013·International Review of Psychiatry·Andrea Gaedigk
Sep 25, 2018·Journal of Clinical Pharmacology·John van den AnkerGregory L Kearns
Dec 18, 2009·Journal of Breath Research·Anil S Modak
Nov 10, 2009·Expert Review of Molecular Diagnostics·Anil S Modak
Jun 11, 2014·British Journal of Clinical Pharmacology·Rashmi R Shah, Robert L Smith
Nov 2, 2014·Journal of Breath Research·Veronika RuzsanyiAnton Amann
Mar 17, 2011·Expert Review of Molecular Diagnostics·Anton AmannAntonio Mutti
Nov 1, 2010·Personalized Medicine·Anil S Modak
Feb 26, 2015·Pharmacogenetics and Genomics·Stephanie L SafgrenMatthew P Goetz

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