التفاصيل البيبلوغرافية
| العنوان: |
Characterization of Human Liver Cytochrome P-450 Enzymes Involved in the O-demethylation of a New P-glycoprotein Inhibitor HM-30181. |
| المؤلفون: |
In Bok Paek, Sung Yeon Kim, Maeng Sup Kim, Kim, John, Gwansun Lee, Hye Suk Lee |
| المصدر: |
Journal of Toxicology & Environmental Health: Part A; Aug2007, Vol. 70 Issue 15/16, p1356-1364, 9p, 1 Diagram, 3 Charts, 5 Graphs |
| مصطلحات موضوعية: |
CYTOCHROME P-450, GLYCOPROTEINS, LIVER, PACLITAXEL, PHARMACOKINETICS, ISOENZYMES |
| مستخلص: |
HM-30181, 4-oxo-4H-chromene-2-carboxylic acid [2-(2-{4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-phenyl}-2H-tetrazol-5-yl)-4,5-dimethoxy-phenyl]-amide, is a new P-glycoprotein inhibitor with the potential to increase the cytotoxic activity of orally coadministered paclitaxel. This study was performed to characterize human cytochrome P-450 (CYP) enzymes involved in the metabolism of HM-30181 to 4- or 5-O-desmethyl-HM-30181 (M2) and 6- or 7-O-desmethyl-HM-30181 (M3) and to investigate the inhibitory potential of HM-30181 on CYP enzymes in human liver microsomes. CYP3A4 was identified as the major isozyme responsible for the O-demethylation of HM-30181 to M2 and M3 based on the correlation analysis, chemical inhibition and immuno-inhibition study and metabolism in cDNA-expressed human CYP isozymes. HM-30181 itself had no inhibitory effects on CYPs 1A2, 2A6, 2C8, 2C9, 2C19, 2D6, and 3A4 in human liver microsomes, suggesting the possibility that the pharmacokinetics of HM-30181 could be changed with coadministration of known CYP3A4 inducers or inhibitors. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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