Evaluation of transporter-mediated hepatobiliary transport of newly developed 18F-labeled pitavastatin derivative, PTV-F1, in rats by PET imaging.

Evaluation of transporter-mediated hepatobiliary transport of newly developed 18F-labeled pitavastatin derivative, PTV-F1, in rats by PET imaging. Drug Metab Pharmacokinet. 2019 Jun 04;: Authors: Kimura H, Yagi Y, Mikamo M, Kazuya M, Kagawa S, Arimitsu K, Higashi T, Nishii R, Ono M, Nakamoto Y, Togashi K, Kusuhara H, Saji H Abstract 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 ...
Source: Drug Metabolism and Pharmacokinetics - Category: Drugs & Pharmacology Tags: Drug Metab Pharmacokinet Source Type: research