モルヒネのグルクロン酸抱合阻害による薬物相互作用の予測
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概要
- 論文の詳細を見る
Morphine is an analgesic drug used for the treatment of acute and chronic pain syndromes for cancer patients. Glucuronidation is a major pathway of the elimination of morphine in humans. Morphine is metabolized to 3-glucuronide (no analgesic effect) and 6-glucuronide (more potently analgesic than morphine) mainly by UGT2B7. In the present study, we investigated the inhibitory effects of a variety of drugs on the morphine glucuronosyltransferase activities in human liver microsomes. Twenty-one drugs including anticancer drugs, immunosuppressants, analgesics, anticonvulsants, antidepressants, antipsychotic drugs were selected in this study, because they are frequently co-administered with morphine. We found that 10 out of 21 drugs, tamoxifen, tacrolimus, diclofenac, carbamazepine, imipramine, clomipramine, amitriptyline, diazepam, lorazepam and oxazepam extensively inhibited the morphine 3- and 6-glucuronosyltransferase activities. Although some of the drugs are not substrates of UGT2B7, they would be potent inhibitors of UGT2B7. If patients receive morphine and these drugs simultaneously, the drug-drug interaction may change the levels of morphine and these glucuronides, resulting in altered analgesic efficacy and the risk of side effects. The results presented here will assist clinicians in choosing the proper drugs and/or dosages, and enable them to anticipate potential drug-drug interactions.
- 日本薬物動態学会=Japanese Society for the Study of Xenobiotics (JSSX)の論文
- 2007-04-25
著者
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中島 美紀
金沢大学 大学院医学系研究科薬物代謝化学
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Nakajima Miki
金沢大学 薬学部薬物代謝化学研究室
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中島 美紀
金沢大学薬学部薬物代謝化学教室
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Nakajima Miki
Drug Metabolism And Toxicology Faculty Of Pharmaceutical Sciences Kanazawa University
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Nakajima Miki
Faculty Of Pharmaceutical Sciences Kanazawa University
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Nakajima Miki
Laboratory Of Drug Metabolism Graduate School Of Pharmaceutical Sciences Hokkaido University
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Hara Yusuke
金沢大学 医学系研究科薬物代謝化学
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Hara Yusuke
Drug Metabolism And Toxicology Division Of Pharmaceutical Sciences Graduate School Of Medical Scienc
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MIYAMOTO Ken-ichi
Kanazawa University Hospital
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YOKOI Tsuyoshi
Drug Metabolism and Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medical Scie
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中島 美紀
金沢大学大学院医学系研究科:金沢大学大学院薬学部
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中島 美紀
金沢大学大学院医学系研究科
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Nakajima Miki
Drug Metabolism And Toxicology Division Of Pharmaceutical Sciences Graduate School Of Medical Scienc
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Yokoi Tsuyoshi
Drug Metabolism And Toxicology Division Of Pharmaceutical Sciences Graduate School Of Medical Scienc
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