YEARS

2004-2007

AUTHORS

Mitchell R Zakin

TITLE

Breath Test to Rapidly Evaluate 2D6 Enzyme Activity

ABSTRACT

DESCRIPTION (provided by applicant): One important consequence of inter-individual variability in drug disposition and response is the risk of adverse drug reactions. In the case of pharmacogenetic variability, genotypic and phenotypic characterization of individual patients or patient populations is of interest in an attempt to predict enzyme activity and potentially optimize drug safety and efficacy. Cytochrome P450 2D6 (CYP2D6) is a clinically important pathway that has been the subject of intense investigation by virtue of its role in the biotransformation of several commonly administered drugs. The goal of the proposed research is to develop a simple, rapid, noninvasive breath test for CYP2D6 activity based on the ingestion of (O-methyl-13C)-dextromethorphan hydrobromide, a stable isotope labeled (non-radioactive) version of the well-characterized CYP2D6 phenotyping probe, dextromethorphan hydrobromide, and measurement of the 13C02/1 C02 ratio in expired breath using commercially available instrumentation. The Phase I program has three Specific Aims: 1. Produce the labeled CYP2D6 substrate (O-methyl-13C)-dextromethorphan hydrobromide (DM) according to 2003 United States Pharmacopeia standards. 2. Demonstrate (O-methyl-13C)-DM as a phenotyping probe for CYP2D6 activity in vivo. 3. Characterize the population distribution of CYP2D6 phenotypes using the breath test. The proposed program is a collaborative effort between Physical Sciences Inc., Cambridge Isotope Laboratories, and J. Steven Leeder, Pharm.D., Ph.D in the Section of Developmental Pharmacology and Therapeutics, Children's Mercy Hospital and Clinics, Kansas City MO.

FUNDED PUBLICATIONS

  • Evaluation of a [13C]-dextromethorphan breath test to assess CYP2D6 phenotype.
  • Evaluation of CYP2D6 enzyme activity using a 13C-dextromethorphan breath test in women receiving adjuvant tamoxifen.
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    19 TRIPLES      17 PREDICATES      20 URIs      9 LITERALS

    Subject Predicate Object
    1 grants:9abd77dcf3d58e934e406f0839dcbc0b sg:abstract DESCRIPTION (provided by applicant): One important consequence of inter-individual variability in drug disposition and response is the risk of adverse drug reactions. In the case of pharmacogenetic variability, genotypic and phenotypic characterization of individual patients or patient populations is of interest in an attempt to predict enzyme activity and potentially optimize drug safety and efficacy. Cytochrome P450 2D6 (CYP2D6) is a clinically important pathway that has been the subject of intense investigation by virtue of its role in the biotransformation of several commonly administered drugs. The goal of the proposed research is to develop a simple, rapid, noninvasive breath test for CYP2D6 activity based on the ingestion of (O-methyl-13C)-dextromethorphan hydrobromide, a stable isotope labeled (non-radioactive) version of the well-characterized CYP2D6 phenotyping probe, dextromethorphan hydrobromide, and measurement of the 13C02/1 C02 ratio in expired breath using commercially available instrumentation. The Phase I program has three Specific Aims: 1. Produce the labeled CYP2D6 substrate (O-methyl-13C)-dextromethorphan hydrobromide (DM) according to 2003 United States Pharmacopeia standards. 2. Demonstrate (O-methyl-13C)-DM as a phenotyping probe for CYP2D6 activity in vivo. 3. Characterize the population distribution of CYP2D6 phenotypes using the breath test. The proposed program is a collaborative effort between Physical Sciences Inc., Cambridge Isotope Laboratories, and J. Steven Leeder, Pharm.D., Ph.D in the Section of Developmental Pharmacology and Therapeutics, Children's Mercy Hospital and Clinics, Kansas City MO.
    2 sg:endYear 2007
    3 sg:fundingAmount 407802.0
    4 sg:fundingCurrency USD
    5 sg:hasContribution contributions:984e8a9cb9f26e547f1b6be2d70fff96
    6 sg:hasFieldOfResearchCode anzsrc-for:11
    7 anzsrc-for:1115
    8 sg:hasFundedPublication articles:7eb71bc30498c74b78d4e0c840f7116f
    9 articles:a42f300b089276f8a48f8f2182c225b1
    10 sg:hasFundingOrganization grid-institutes:grid.48336.3a
    11 sg:hasRecipientOrganization grid-institutes:grid.280671.a
    12 sg:language English
    13 sg:license http://scigraph.springernature.com/explorer/license/
    14 sg:scigraphId 9abd77dcf3d58e934e406f0839dcbc0b
    15 sg:startYear 2004
    16 sg:title Breath Test to Rapidly Evaluate 2D6 Enzyme Activity
    17 sg:webpage http://projectreporter.nih.gov/project_info_description.cfm?aid=6947939
    18 rdf:type sg:Grant
    19 rdfs:label Grant: Breath Test to Rapidly Evaluate 2D6 Enzyme Activity
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