Metabolic Fate of Pitavastatin (NK-104), a New Inhibitor of 3-Hydroxy-3-methyllutaryl Coenzyme A Reductase
| العنوان: | Metabolic Fate of Pitavastatin (NK-104), a New Inhibitor of 3-Hydroxy-3-methyllutaryl Coenzyme A Reductase |
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| المؤلفون: | Hideki Fujino, Syunsuke Shimada, Michiaki Yoneda, Takeshi Nagao, Iwao Yamada |
| المصدر: | Arzneimittelforschung. 52:745-753 |
| بيانات النشر: | Georg Thieme Verlag KG, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | medicine.medical_specialty, Unspecific monooxygenase, biology, Metabolite, Reductase, Hydroxymethylglutaryl-CoA reductase, chemistry.chemical_compound, Endocrinology, chemistry, Enzyme inhibitor, Internal medicine, Drug Discovery, HMG-CoA reductase, biology.protein, medicine, Pitavastatin, Drug metabolism, medicine.drug |
| الوصف: | Pitavastatin (CAS 147526-32-7, NK-104) is a new and very potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and has been approved for treatment of hyperlipoproteinaemia. Pitavastatin has been studied for its effects on hepatic microsomal drug metabolism in rats, and the activities of several drug-metabolizing enzymes have been measured. No induction of the drug metabolizing enzymes (aniline hydroxylase, aminopyrine N-demethylase, 7-ethoxycoumarin O-deethylase and UDP-glucuronic acid transferase) was found in the pitavastatin group compared to the control after the multiple administrations of pitavastatin at the dosage of 1–10 mg/kg per day for 7 days. Based on several different in vitro approaches, it is concluded that CYP2C9 is the enzyme responsible for the metabolism of pitavastatin and no metabolite is present in renal and intestinal microsomes. The CYP2C9 polymorphism was not involved in the pitavastatin metabolism. No inhibitory effect in CYP-mediated metabolism was detected on the tolbutamide 4-hydroxylation (CYP2C9) and testosterone 6β-hydroxylation (CYP3A4) in the presence of pitavastatin. The results suggested that pitavastatin did not affect the drug-metabolizing systems. |
| تدمد: | 1616-7066 0004-4172 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::d60b73e29de89b07c7fbce6dc5d35cad https://doi.org/10.1055/s-0031-1299961 |
| رقم الأكسشن: | edsair.doi...........d60b73e29de89b07c7fbce6dc5d35cad |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16167066 00044172 |
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