74 research outputs found
Identification des voies métaboliques hépatiques d'un agent anticancéreux (la méthoxymorpholino doxorubicine ; étude d'interactions médicamenteuses (doctorat : sciences de la vie et de la sante))
BREST-BU MĂ©decine-Odontologie (290192102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Both cytochromes P450 1A and 3A4 are involved in the N-demethylation of tamoxifen
info:eu-repo/semantics/publishe
Toxicity and metabolism of tamoxifen in primary rat hepatocyte cultures
info:eu-repo/semantics/nonPublishe
Identification of the UDP-glucuronosyltransferase isoforms involved in mycophenolic acid phase II metabolism. Drug Metab Dispos
ABSTRACT: Mycophenolic acid (MPA), the active metabolite of the immunosuppressant mycophenolate mofetil is primarily metabolized by glucuronidation. The nature of UDP-glucuronosyltransferases (UGTs) involved in this pathway is still debated. The present study aimed at identifying unambiguously the UGT isoforms involved in the production of MPA-phenyl-glucuronide (MPAG) and MPA-acylglucuronide (AcMPAG). A liquid chromatography-tandem mass spectrometry method allowing the identification and determination of the metabolites of mycophenolic acid was developed. The metabolites were characterized in urine and plasma samples from renal transplant patients under mycophenolate mofetil therapy and in vitro after incubation of mycophenolic acid with human liver (HLM), kidney (HKM), or intestinal microsomes (HIM). The UGT isoforms involved in MPAG or AcMPAG production were investigated using induced rat liver microsomes, heterologously expressed UGT (Supersomes), and chemical-selective inhibition of HLM, HKM, and HIM. The three microsomal preparations produced MPAG, AcMPAG, and two mycophenolate glucosides. Among the 10 UGT isoforms tested, UGT 1A9 was the most efficient for MPAG synthesis with a K m of 0.16 mM, close to that observed for HLM (0.18 mM). According to the chemical inhibition experiments, UGT 1A9 is apparently responsible for 55%, 75%, and 50% of MPAG production by the liver, kidney, and intestinal mucosa, respectively. Although UGT 2B7 was the only isoform producing AcMPAG in a significant amount, the selective inhibitor azidothymidine only moderately reduced this production (approximately Ű25%). In conclusion, UGT 1A9 and 2B7 were clearly identified as the main UGT isoforms involved in mycophenolic acid glucuronidation, presumably due to their high hepatic and renal expression
Identification of the UDP-glucuronosyltransferase isoforms involved in mycophenolic acid phase II metabolism. Drug Metab Dispos
Effect of retinol and retinoic acid supplemented diets on cytochrome Pâ450 content and UDP glucuronosyltransferase activities in vitamin Aâdeficient rat liver
Intravenous and Oral Propafenone for Treatment of Tachycardia in Infants and Children: Pharmacokinetics and Clinical Response
Lâapproche de la notion de critĂšre de jugement principal par les Ă©tudiants lors de lâĂ©preuve de lecture critique dâarticle au cours des Ă©preuves classantes nationales 2010
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