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Effect of Chronic Kidney Disease on Hepatic Clearance of Drugs in Rats
http://hdl.handle.net/10069/40283
http://hdl.handle.net/10069/402835127cc66-cdd7-48a4-a441-f20fe289ccb0
名前 / ファイル | ライセンス | アクション |
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BPBul43_1324.pdf (601.2 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2020-09-24 | |||||
タイトル | ||||||
タイトル | Effect of Chronic Kidney Disease on Hepatic Clearance of Drugs in Rats | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | acetaminophen | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | chronic kidney disease | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | indocyanine green | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | midazolam | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | pharmacokinetics | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Tokunaga, Ayako
× Tokunaga, Ayako× Miyamoto, Hirotaka× Fumoto, Shintaro× Nishida, Koyo |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | The pharmacokinetics of some hepatically cleared drugs have been reported to fluctuate in patients with renal impairment, but the definitive factors have not been clarified. We compared the pharmacokinetics of some drugs with different hepatic elimination processes in a chronic kidney disease (CKD) rat model, to optimize their administration during kidney injury. We chose indocyanine green (ICG), midazolam (MDZ), and acetaminophen (APAP) as reference drugs to determine changes in hepatic clearance pathways in presence of CKD. Drugs were intravenously administered via the jugular vein to the CKD model rats, previously established by adenine administration, and then, blood, bile, and urine samples were collected. The plasma concentration of ICG, which is eliminated into the bile without biotransformation, increased; and its total body clearance (CLtot) significantly decreased in the CKD group compared to the control group.Moreover, the plasma concentrations of MDZ and APAP, metabolized in the liver by CYP3A and Ugt1a6 enzymes, respectively, were higher in the CKD group than in the control group. The biliary clearances of APAP and its derivative APAP-glucuronide increased in the CKD group, whereas their renal clearances were markedly decreased with respect to those in the control group. Altogether, plasma concentrations of some hepatically eliminated drugs increased in the CKD rat model, but depending on their pharmacokinetic characteristics. This study provides useful information for optimizing the administration of some hepatically cleared drugs in CKD patients. |
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書誌情報 |
Biological and Pharmaceutical Bulletin 巻 43, 号 9, p. 1324-1330, 発行日 2020-09-01 |
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出版者 | ||||||
出版者 | 日本薬学会 | |||||
出版者別言語 | ||||||
The Pharmaceutical Society of Japan | ||||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 09186158 | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 13475215 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1248/bpb.b20-00124 | |||||
権利 | ||||||
権利情報 | c 2020 The Pharmaceutical Society of Japan | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Biological & Pharmaceutical Bulletin, 43(9), pp.1324-1330; 2020 |