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.
Guilluy
R
R
L.E.A.C.M., Laboratoire d'Etudes Analytiques et Cinétiques du Médicament, Institut des Sciences Pharmaceutiques et Biologiques de Lyon, France.
Billion-Rey
F
F
Brazier
J L
JL
D000818:Animals; D001944:Breath Tests / Q000379:methods*; D002110:Caffeine / Q000494:pharmacology; D002245:Carbon Dioxide / Q000032:analysis; D002247:Carbon Isotopes; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects*; D008401:Gas Chromatography-Mass Spectrometry; D007700:Kinetics; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats
D002247:Carbon Isotopes; D002245:Carbon Dioxide; D002110:Caffeine; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital