Single time point diagnostic breath tests: a review

Abstract

The metabolism of ingested xenobiotics is clinically significant to minimize risk and optimize therapeutic benefits. A majority of the drugs approved by the FDA are metabolized by phase I enzymes. Stable isotope-labeled xenobiotics can be used to provide rapid in vivo phenotype assessment of phase I enzymes. In this paper, we describe three simple, noninvasive phenotype breath tests using [13C]-dextromethorphan and [13C]-pantoprazole for assessing polymorphic CYP2D6 and CYP2C19 enzyme activity and [13C]-uracil to assess the enzyme activity of DPD, DPHD and β-ureidopropionase for identifying pyrimidine metabolic disorder. The results of the [13C]-dextromethorphan, [13C]-pantoprazole and [13C]-uracil breath test studies suggest that they have great potential for evaluating CYP2D6, CYP2C19 and DPD enzyme activities in a relatively short time with a single time point breath collection in a clinic or hospital setting. This would enable physicians to prescribe personalized therapy for each individual by selecting the ideal medication at the right dose for optimal efficacy of xenobiotics metabolized by these enzymes.