| The disposition of pravastatin in a rat model of streptozotocin-induced diabetes and organic anion transporting polypeptide 2 and multidrug resistance-associated protein 2 expression in the liver. | |
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MedLine Citation:
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PMID: 20045956 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The combination of diabetes and hyperlipidemia promotes the development of atherosclerosis. Therefore, it is important for diabetic patients to control blood fat. 3-Hydroxy-3-methylglutaryl enzyme A (HMG-CoA) reductase inhibitors (statins), like pravastatin, are frequently administered to diabetic patients for this purpose. Although the alterations of metabolic enzymes and transporters in the diabetic liver maybe change the disposition of pravastatin, the effect has not been fully investigated. In the present study, we investigated the disposition of pravastatin and the mRNA expression of transporters in the liver. Pravastatin (5 mg.kg(-1) body weight) was administered intravenously to diabetic rats, and the pravastatin concentrations in the plasma, urine, and bile were measured by high-performance liquid chromatography. Changes in the mRNA expressions of multidrug resistance-associated protein 2 (MRP2) and organic anion transporting polypeptide 2 (OATP2) in the liver were also estimated using reverse transcriptase-polymerase chain reaction (RT-PCR). We found that the plasma pravastatin concentration was lower in the diabetic rat because the transportation of pravastatin into hepatocytes was promoted along with increased expression of OATP2. The biliary excretion ratio of pravastatin was significantly lower in the diabetic rat because the pravastatin transportation into bile was reduced along with the decreased expression of MRP2. To clarify these phenomena, the analysis of mRNA expression using real-time PCR and the measurement of the amount and the activity of proteins are necessary in future study. |
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Authors:
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Yoshitaka Hasegawa; Shuichi Kishimoto; Naoki Shibatani; Nobuo Inotsume; Yoshikazu Takeuchi; Shoji Fukushima |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Biological & pharmaceutical bulletin Volume: 33 ISSN: 1347-5215 ISO Abbreviation: Biol. Pharm. Bull. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-04 Completed Date: 2010-06-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9311984 Medline TA: Biol Pharm Bull Country: Japan |
Other Details:
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Languages: eng Pagination: 153-6 Citation Subset: IM |
Affiliation:
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Laboratory of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Area Under Curve Bile / metabolism Biological Transport Chromatography, High Pressure Liquid Diabetes Mellitus, Experimental / metabolism* Gene Expression Liver / metabolism* Male Multidrug Resistance-Associated Proteins / genetics, metabolism* Organic Anion Transporters / genetics, metabolism* Pravastatin / administration & dosage, blood, pharmacokinetics* RNA, Messenger / metabolism Rats Rats, Inbred Strains Reverse Transcriptase Polymerase Chain Reaction |
| Chemical | |
Reg. No./Substance:
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0/Multidrug Resistance-Associated Proteins; 0/Organic Anion Transporters; 0/RNA, Messenger; 0/multidrug resistance-associated protein 2; 81093-37-0/Pravastatin |
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