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Preclinical evaluation of [18F]LCATD as a PET tracer to study drug-drug interactions caused by inhibition of hepatic transporters
The bile acid analogue [18F]LCATD (LithoCholic Acid Triazole Derivative) is transported in vitro by hepatic uptake transporters such as OATP1B1 and NTCP and efflux transporter BSEP. In this in vivo "proof of principle" study, we tested if [18F]LCATD may be used to evaluate drug-drug intera...
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| Format: | Default Article |
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2018
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| Online Access: | https://hdl.handle.net/2134/36581 |
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| _version_ | 1818168923615395840 |
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| author | Andrea Testa Sergio Dall'Angelo Marco Mingarelli Andrea Augello Lutz Schweiger Andrew Welch Charles S. Elmore Dana Dawson Pradeep Sharma Matteo Zanda |
| author_facet | Andrea Testa Sergio Dall'Angelo Marco Mingarelli Andrea Augello Lutz Schweiger Andrew Welch Charles S. Elmore Dana Dawson Pradeep Sharma Matteo Zanda |
| author_sort | Andrea Testa (2096059) |
| collection | Figshare |
| description | The bile acid analogue [18F]LCATD (LithoCholic Acid Triazole Derivative) is transported in vitro by hepatic uptake transporters such as OATP1B1 and NTCP and efflux transporter BSEP. In this in vivo "proof of principle" study, we tested if [18F]LCATD may be used to evaluate drug-drug interactions (DDIs) caused by inhibition of liver transporters. Hepatic clearance of [18F]LCATD in rats was significantly modified upon coadministration of rifamycin SV or sodium fusidate, which are known to inhibit clinically relevant uptake transporters (OATP1B1, NTCP) and canalicular hepatic transporters (BSEP) in humans. Treatment with rifamycin SV (total dose 62.5 mg·Kg-1) reduced the maximum radioactivity of [18F]LCATD recorded in the liver from 14.2 ± 0.8% to 10.2 ± 0.9% and delayed t-max by 90 seconds relative to control rats. AUCliver 0-5 min, AUCbile 0-10 min and hepatic uptake clearance CLuptake,in vivo of rifamycin SV treated rats were significantly reduced, whereas AUCliver 0-30 min was higher than in control rats. Administration of sodium fusidate (30 mg·Kg-1) inhibited the liver uptake of [18F]LCATD, although to a lesser extent, reducing the maximum radioactivity in the liver to 11.5 ± 0.3%. These preliminary results indicate that [18F]LCATD may be a good candidate for future applications as an investigational tracer to evaluate altered hepatobiliary excretion as a result of drug-induced inhibition of hepatic transporters. |
| format | Default Article |
| id | rr-article-9391406 |
| institution | Loughborough University |
| publishDate | 2018 |
| record_format | Figshare |
| spelling | rr-article-93914062018-01-01T00:00:00Z Preclinical evaluation of [18F]LCATD as a PET tracer to study drug-drug interactions caused by inhibition of hepatic transporters Andrea Testa (2096059) Sergio Dall'Angelo (7162667) Marco Mingarelli (196827) Andrea Augello (7163447) Lutz Schweiger (7163450) Andrew Welch (7163453) Charles S. Elmore (2004724) Dana Dawson (7020656) Pradeep Sharma (59873) Matteo Zanda (5569472) Other chemical sciences not elsewhere classified untagged Chemical Sciences not elsewhere classified The bile acid analogue [18F]LCATD (LithoCholic Acid Triazole Derivative) is transported in vitro by hepatic uptake transporters such as OATP1B1 and NTCP and efflux transporter BSEP. In this in vivo "proof of principle" study, we tested if [18F]LCATD may be used to evaluate drug-drug interactions (DDIs) caused by inhibition of liver transporters. Hepatic clearance of [18F]LCATD in rats was significantly modified upon coadministration of rifamycin SV or sodium fusidate, which are known to inhibit clinically relevant uptake transporters (OATP1B1, NTCP) and canalicular hepatic transporters (BSEP) in humans. Treatment with rifamycin SV (total dose 62.5 mg·Kg-1) reduced the maximum radioactivity of [18F]LCATD recorded in the liver from 14.2 ± 0.8% to 10.2 ± 0.9% and delayed t-max by 90 seconds relative to control rats. AUCliver 0-5 min, AUCbile 0-10 min and hepatic uptake clearance CLuptake,in vivo of rifamycin SV treated rats were significantly reduced, whereas AUCliver 0-30 min was higher than in control rats. Administration of sodium fusidate (30 mg·Kg-1) inhibited the liver uptake of [18F]LCATD, although to a lesser extent, reducing the maximum radioactivity in the liver to 11.5 ± 0.3%. These preliminary results indicate that [18F]LCATD may be a good candidate for future applications as an investigational tracer to evaluate altered hepatobiliary excretion as a result of drug-induced inhibition of hepatic transporters. 2018-01-01T00:00:00Z Text Journal contribution 2134/36581 https://figshare.com/articles/journal_contribution/Preclinical_evaluation_of_18F_LCATD_as_a_PET_tracer_to_study_drug-drug_interactions_caused_by_inhibition_of_hepatic_transporters/9391406 CC BY 4.0 |
| spellingShingle | Other chemical sciences not elsewhere classified untagged Chemical Sciences not elsewhere classified Andrea Testa Sergio Dall'Angelo Marco Mingarelli Andrea Augello Lutz Schweiger Andrew Welch Charles S. Elmore Dana Dawson Pradeep Sharma Matteo Zanda Preclinical evaluation of [18F]LCATD as a PET tracer to study drug-drug interactions caused by inhibition of hepatic transporters |
| title | Preclinical evaluation of [18F]LCATD as a PET tracer to study drug-drug interactions caused by inhibition of hepatic transporters |
| title_full | Preclinical evaluation of [18F]LCATD as a PET tracer to study drug-drug interactions caused by inhibition of hepatic transporters |
| title_fullStr | Preclinical evaluation of [18F]LCATD as a PET tracer to study drug-drug interactions caused by inhibition of hepatic transporters |
| title_full_unstemmed | Preclinical evaluation of [18F]LCATD as a PET tracer to study drug-drug interactions caused by inhibition of hepatic transporters |
| title_short | Preclinical evaluation of [18F]LCATD as a PET tracer to study drug-drug interactions caused by inhibition of hepatic transporters |
| title_sort | preclinical evaluation of [18f]lcatd as a pet tracer to study drug-drug interactions caused by inhibition of hepatic transporters |
| topic | Other chemical sciences not elsewhere classified untagged Chemical Sciences not elsewhere classified |
| url | https://hdl.handle.net/2134/36581 |