Linked Life Data

17267620

Source:http://linkedlifedata.com/resource/pubmed/id/17267620

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-3-26
pubmed:abstractText
Hepatocytes and liver microsomes are considered to be useful for investigating drug metabolism catalyzed mainly via glucuronidation. However, there have been few reports comparing the glucuronidation inhibition potentials of drug in hepatocytes to those in liver microsomes. 3'-Azido-3'-deoxythymidine (AZT, zidovudine) glucuronidation (AZTG) is the major metabolic pathway for AZT. In this study, the inhibition potentials of drugs against UDP-glucuronosyltransferase (UGT)-catalyzed AZTG in the hepatocytes and liver microsomes of rats are compared. The AZTG inhibition potentials of diclofenac, diflunisal, fluconazole, indomethacin, ketoprofen, mefenamic acid, naproxen, niflumic acid, and valproic acid in liver microsomes and hepatocytes were investigated using liquid chromatography with tandem mass spectrometry. Diflunisal (inhibition type: noncompetitive) inhibited AZTG most potently in rat liver microsomes (RLMs) with an IC(50) value of 34 microM. The IC(50) values of diclofenac, fluconazole, indomethacin, ketoprofen, mefenamic acid, naproxen, niflumic acid, and valproic acid against AZTG in RLMs ranged from 34 to 1791 microM. Diclofenac, diflunisal, indomethacin, ketoprofen, naproxen, and valproic acid inhibited AZTG in hepatocytes with IC(50) values of 58, 37, 88, 361, 486, and 281 microM, respectively. These values were similar to those obtained in RLMs. In conclusion, the AZT glucuronidation inhibition potentials of drugs in the hepatocytes and liver microsomes of rats were found to be similar, and liver microsomes can be useful for evaluating UGT isozyme inhibition potentials.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
602-6
pubmed:meshHeading
pubmed-meshheading:17267620-Animals, pubmed-meshheading:17267620-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:17267620-Anticonvulsants, pubmed-meshheading:17267620-Antifungal Agents, pubmed-meshheading:17267620-Chromatography, High Pressure Liquid, pubmed-meshheading:17267620-Dose-Response Relationship, Drug, pubmed-meshheading:17267620-Drug Evaluation, Preclinical, pubmed-meshheading:17267620-Drug Interactions, pubmed-meshheading:17267620-Enzyme Inhibitors, pubmed-meshheading:17267620-Glucuronides, pubmed-meshheading:17267620-Glucuronosyltransferase, pubmed-meshheading:17267620-Hepatocytes, pubmed-meshheading:17267620-Microsomes, Liver, pubmed-meshheading:17267620-Molecular Structure, pubmed-meshheading:17267620-Rats, pubmed-meshheading:17267620-Reverse Transcriptase Inhibitors, pubmed-meshheading:17267620-Tandem Mass Spectrometry, pubmed-meshheading:17267620-Uridine Diphosphate Glucuronic Acid, pubmed-meshheading:17267620-Zidovudine
pubmed:year
2007
pubmed:articleTitle
Comparison of inhibition potentials of drugs against zidovudine glucuronidation in rat hepatocytes and liver microsomes.
pubmed:affiliation
Drug Metabolism Research Laboratories, Astellas Pharma Inc., 1-8, Azusawa 1-Chome, Itabashi-ku, Tokyo, 174-8511, Japan. yuuji.mano@jp.astellas.com
pubmed:publicationType
Journal Article, Comparative Study