ONLINE MEASUREMENTS OF C-13 ENRICHMENTS IN RAT BREATH NONINVASIVE METHOD FOR INVIVO STUDY OF DRUG ENZYMATIC INDUCTION

A differential kinetic study of (CO2)-C-13 enrichment of breath after the intake of specific C-13-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 (CO2)-C-13 enrichment on 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 (CO2)-C-13 enrichment by isotope ratio mass spectrometry. Two protocols for phenobarbital-inducible P450 and 3-methylcholanthrene-inducible P1-450 isoenzymes are described.