[Metabolism of nicousamide in rat and human liver in vitro].
This paper is aimed to study the metabolic kinetics of nicousamide in rat liver microsomes and cytosol and to identify the major metabolite and drug metabolizing enzymes involved in the metabolism of nicousamide in rat and human liver microsomes by selective inhibitors in vitro. The concentration of nicousamide was determined by HPLC-UV method. The metabolite of nicousamide in rat and human liver microsomes was isolated and identified by LC-MS/MS. The major metabolite of nicousamide in rat and human liver microsomes was identified to be 3-(3'-carboxy-4'-hydroxy-anilino-carbo-)-6-amino-7-hydroxy-8-methyl-coumarin (M1). The metabolite of nicousamide in rat plasma, urine, bile and liver was consistent with M1. The metabolism of nicousamide can be catalyzed by several reductases, including CYP450 reductases, cytochrome b5 reductases and CYP2C6 in rat liver microsomes, as well as xanthine oxidase and DT-diaphorase in rat liver cytosol.
Sheng
Li
L
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Hu
Jin-ping
JP
Chen
Hui
H
Li
Yan
Y
D000249:Adenosine Monophosphate / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D003374:Coumarins / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors; D000072467:Cytochrome P450 Family 2; D042966:Cytochrome-B(5) Reductase / Q000037:antagonists & inhibitors; D003600:Cytosol / Q000378:metabolism; D001728:Dicumarol / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors; D011441:Propylthiouracil / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013255:Steroid 21-Hydroxylase / Q000037:antagonists & inhibitors; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D000814:Aniline Compounds; D003374:Coumarins; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; C523324:nicousamide; D000249:Adenosine Monophosphate; D000493:Allopurinol; D011441:Propylthiouracil; D001728:Dicumarol; D002927:Cimetidine; C089877:Cyp2c6v1 protein, rat; D000072467:Cytochrome P450 Family 2; D013255:Steroid 21-Hydroxylase; D014969:Xanthine Oxidase; D042966:Cytochrome-B(5) Reductase; D016660:NAD(P)H Dehydrogenase (Quinone)