¹³C - Dextromethorphan (DM) Breath Test for Determination of CYP2D6 Enzyme Activity in Patients Receiving Tamoxifen
- To assess the operating characteristics of the ¹³C-dextromethorphan (^13 C-DM) breath
test in identifying women with breast cancer (or at high risk) who are CYP2D6-genotypic
- To examine the correlation between CYP2D6 enzyme activity (as measured by the breath
test) and plasma endoxifen (and 4-hydroxyTAM) levels in patients who carry one or more
CYP2D6 functional alleles.
- To examine the change in CYP2D6 enzyme activity (as measured by the ¹³C-DM breath
test), in patients who start a CYP2D6 inhibitor while taking tamoxifen.
- To determine whether CYP2D6 enzyme activity (as measured by the breath test) changes
over time (either as a consequence of drug-induced inhibition or other).
- To measure genetic variation in additional genes that are later identified to affect
the metabolism, uptake, or distribution of tamoxifen (e.g., SULT1A1, UGT).
OUTLINE: Patients receive tamoxifen citrate for 6 months. ^13C-dextromethorphan breath tests
are conducted at baseline and periodically during the 6 months.
13C-dextromethorphan breath test: Patients receive oral Alka-Seltzer® Gold (ASG; citric
acid, potassium bicarbonate, and sodium bicarbonate) in water, then, 15 minutes later,
another ASG dose and oral ¹³C-dextromethorphan. Patients breathe into a bag 1-2 times, and
the is bag sealed. ¹³CO_2 levels in the bags are measured.
Blood samples are collected at baseline and periodically for pharmacogenetic and
pharmacokinetic studies by reverse phase HPLC with fluorescence detection.
After completion of study therapy, patients are followed annually for 5 years.
Masking: Open Label, Primary Purpose: Diagnostic
Operating characteristics of the ¹³C-dextromethorphan (13C-DM) breath test in identifying those who are CYP2D6 genotypic poor metabolizers
Matthew P. Goetz, M.D.
United States: Food and Drug Administration
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