caa a22 4500 469026227 CHVBK 20180323132730.0 cr unu---uuuuu 170328e19920601xx s 000 0 eng 10.1007/BF01962707 doi (NATIONALLICENCE)springer-10.1007/BF01962707 Δ2-Valproate biotransformation using human liver microsomal fractions [Elektronische Daten] [Gérard Fabre, Christophe Briot, Eric Marti, Jean Montseny, Martine Bourrié, Danielle Massé, Yves Berger, Jean Cano] The metabolism of 2-n-propyl-2-pentenoate (Δ2-VPA) was evaluated in human hepatic microsomal fractions. Two biotransformation pathways have been particularly investigated. In the presence of the cytochrome P-450 co-factor, NADPH, the main metabolites recovered were Δ3-VPA, Δ2,4-VPA and VPA. The glucuronidation of Δ2-VPA was also studied on various hepatic microsomal fractions using Brij® 35 as activator and UDP-glucuronic acid as co-factor. A large interindividual variability occurred in this metabolic pathway.K m andV max were 0.85 mmol/l and 1.75 nmol·min−1·mg−1, respectively, for Δ2-VPA and 1.11 mmol/l and 5.71 nmol·min−1·mg−1 for VPA, respectively. The good correlationr=0.82; p<0.001) observed between the glucuronidation of VPA and Δ2-VPA as well as the mutual inhibition of each other's glucuronidation strongly suggests that (a) common single UDP-glucuronosyltransferase isoenzyme(s) was (were) involved in this glucuronidation step. The glucuronidation of specific substrates for various UDP-glucuronosyltransferase isoenzymes showed a good relationship between the glucuronidations of Δ2-VPA and morphine, a substrate for UDP-glucuronosyltransferase-2B. Moreover, morphine competitively inhibits A -VPA glucuronidation. It seems the same isoenzyme or, at least, (a) very closely related isoenzyme(s) belonging to UDP-glucuronosyltransferase-2 isoenzyme, is involved in Δ2-VPA glucuronidation. Royal Dutch Association for Advancement of Pharmacy, 1992 Biotransformation nationallicence Cytochrome P-450 nationallicence Isoenzymes nationallicence Microsomes, liver nationallicence 2- n -Propyl-2-pentenoic acid nationallicence UDP glucuronosyltransferase nationallicence Valproic acid nationallicence Fabre Gérard Sanofi Recherche, 371 Rue du Professeur Blayac, 34184, Montpellier, Cédex 04, France aut Briot Christophe Sanofi Recherche, 371 Rue du Professeur Blayac, 34184, Montpellier, Cédex 04, France aut Marti Eric Sanofi Recherche, 371 Rue du Professeur Blayac, 34184, Montpellier, Cédex 04, France aut Montseny Jean Sanofi Recherche, 371 Rue du Professeur Blayac, 34184, Montpellier, Cédex 04, France aut Bourrié Martine Sanofi Recherche, 371 Rue du Professeur Blayac, 34184, Montpellier, Cédex 04, France aut Massé Danielle Sanofi Recherche, 371 Rue du Professeur Blayac, 34184, Montpellier, Cédex 04, France aut Berger Yves Sanofi Recherche, 371 Rue du Professeur Blayac, 34184, Montpellier, Cédex 04, France aut Cano Jean Ministère Chargé de la Santé, 8 Avenue de Ségur, 75350, Paris 07 SP, France aut Pharmaceutisch Weekblad Kluwer Academic Publishers 14/3(1992-06-01), 146-151 0031-6911 14:3<146 1992 14 11096 https://doi.org/10.1007/BF01962707 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01962707 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fabre Gérard Sanofi Recherche, 371 Rue du Professeur Blayac, 34184, Montpellier, Cédex 04, France aut NATIONALLICENCE 700 1- Briot Christophe Sanofi Recherche, 371 Rue du Professeur Blayac, 34184, Montpellier, Cédex 04, France aut NATIONALLICENCE 700 1- Marti Eric Sanofi Recherche, 371 Rue du Professeur Blayac, 34184, Montpellier, Cédex 04, France aut NATIONALLICENCE 700 1- Montseny Jean Sanofi Recherche, 371 Rue du Professeur Blayac, 34184, Montpellier, Cédex 04, France aut NATIONALLICENCE 700 1- Bourrié Martine Sanofi Recherche, 371 Rue du Professeur Blayac, 34184, Montpellier, Cédex 04, France aut NATIONALLICENCE 700 1- Massé Danielle Sanofi Recherche, 371 Rue du Professeur Blayac, 34184, Montpellier, Cédex 04, France aut NATIONALLICENCE 700 1- Berger Yves Sanofi Recherche, 371 Rue du Professeur Blayac, 34184, Montpellier, Cédex 04, France aut NATIONALLICENCE 700 1- Cano Jean Ministère Chargé de la Santé, 8 Avenue de Ségur, 75350, Paris 07 SP, France aut NATIONALLICENCE 773 0- Pharmaceutisch Weekblad Kluwer Academic Publishers 14/3(1992-06-01), 146-151 0031-6911 14:3<146 1992 14 11096 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer