On-line measurements of 13C enrichments in rat breath. Non-invasive method for in vivo study of drug enzymatic induction.

A differential kinetic study of 13CO2 enrichment of breath after the intake of specific 13C-labelled substrates and co-administration of a drug allows the drug's ability for enzyme induction to be evaluated in vivo. A method and a gas chromatograph-isotope ratio mass spectrometer device for on-line measurements of 13CO2 enrichment in the breath of small animals are described. This system allows on-line breath sample collection from a metabolic cage, purification by gas chromatography, determination of CO2 by thermal conductivity detection and measurement of 13CO2 enrichment by isotope ratio mass spectrometry. Two protocols for phenobarbital-inducible P450 and 3-methylcholanthrene-inducible P1-450 isoenzymes are described.