Evaluation of transporter-mediated hepatobiliary transport of newly developed ¹⁸F-labeled pitavastatin derivative, PTV-F1, in rats by PET imaging
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Quantitative evaluations of the functions of uptake and efflux transporters directly in vivo is desired to understand an efficient hepatobiliary transport of substrate drugs. Pitavastatin is a substrate of organic anion transporting polypeptides (OATPs) and canalicular efflux transporters; thus, it can be a suitable probe for positron-emission tomography (PET) imaging of hepatic transporter functions. To characterize the performance of [¹⁸F]PTV-F1, an analogue of pitavastatin, we investigated the impact of rifampicin (a typical OATP inhibitor) coadministration or Bcrp (breast cancer resistance protein) knockout on [¹⁸F]PTV-F1 hepatic uptake and efflux in rats by PET imaging. After intravenous administration, [¹⁸F]PTV-F1 selectively accumulated in the liver, and the radioactivity detected in plasma, liver, and bile mainly derived from the parent PTV-F1 during the PET study (∼40 min). Coadministration of rifampicin largely decreased the hepatic uptake of [¹⁸F]PTV-F1 by 73%. Because of its lower clearance in rats, [¹⁸F]PTV-F1 is more sensitive for monitoring changes in hepatic OATP1B function that other previously reported OATP1B PET probes. Rifampicin coadministration also significantly decreased the biliary excretion of radioactivity by 65%. Bcrp knockout did not show a significant impact on its biliary excretion.[¹⁸F]PTV-F1 enables quantitative analysis of the hepatobiliary transport system for organic anions.
収録刊行物
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- Drug Metabolism and Pharmacokinetics
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Drug Metabolism and Pharmacokinetics 34 (5), 317-324, 2019-10
Elsevier BV
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詳細情報 詳細情報について
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- CRID
- 1050001338895248640
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- NII論文ID
- 120006767903
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- NII書誌ID
- AA1162652X
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- ISSN
- 13474367
- 18800920
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- HANDLE
- 2433/244807
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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