Comparison of the metabolism and pharmacokinetics of metbufen and itanoxone and their analogues in rats.
Metbufen, II, itanoxone, I, and two other derivatives of gamma-aryl-gamma-keto-substituted butyric acids labelled with 14C in their carbonyl group were synthesized for a metabolic investigation in rats. Profound changes in pharmacokinetic parameters, most specifically in the distribution, elimination, and metabolic pathways, were induced by substitution in the aromatic nucleus or changes in saturation of the aliphatic chain. The metabolites isolated from plasma and urine were identified by gas chromatography and mass spectrometry, by comparison with chemical controls, revealing the processes of metabolism of these structural analogues. This difference in metabolism further understanding of the diversity of biological effects inherent in these compounds.
Chanal
J L
JL
Physical Laboratory, Faculté de Pharmacie, Montpellier, France.
Audran
M
M
Bret
M C
MC
Cousse
H
H
Fauran
F
F
Rieu
J P
JP
D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000378:metabolism; D002090:Butyrophenones / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D055598:Chemical Phenomena; D002621:Chemistry; D002855:Chromatography, Thin Layer; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D008297:Male; D051381:Rats
D002090:Butyrophenones; D000960:Hypolipidemic Agents; C024140:itanoxone