Search: onr:"swepub:oai:DiVA.org:uu-222386" > Prediction of In Vi...
Fältnamn | Indikatorer | Metadata |
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000 | 03459naa a2200397 4500 | |
001 | oai:DiVA.org:uu-222386 | |
003 | SwePub | |
008 | 140410s2014 | |||||||||||000 ||eng| | |
009 | oai:prod.swepub.kib.ki.se:128378718 | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2223862 URI |
024 | 7 | a https://doi.org/10.1124/dmd.113.0541552 DOI |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1283787182 URI |
040 | a (SwePub)uud (SwePub)ki | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Lundquist, Patriku Uppsala universitet,Institutionen för farmaci4 aut0 (Swepub:uu)patlu774 |
245 | 1 0 | a Prediction of In Vivo Rat Biliary Drug Clearance from an In Vitro Hepatocyte Efflux Model |
264 | c 2014-01-06 | |
264 | 1 | b American Society for Pharmacology & Experimental Therapeutics (ASPET),c 2014 |
338 | a print2 rdacarrier | |
520 | a Well-established techniques are available to predict in vivo hepatic uptake and metabolism from in vitro data, but predictive models for biliary clearance remain elusive. Several studies have verified the expression and activity of ATP-binding cassette (ABC) efflux transporters central to biliary clearance in freshly isolated rat hepatocytes, raising the possibility of predicting biliary clearance from in vitro efflux measurements. In the present study, short-term plated rat hepatocytes were evaluated as a model to predict biliary clearance from in vitro efflux measurements before major changes in transporter expression known to take place in long-term hepatocyte cultures. The short-term cultures were carefully characterized for their uptake and metabolic properties using a set of model compounds. In vitro efflux was studied using digoxin, fexofenadine, napsagatran, and rosuvastatin, representing compounds with over 100-fold differences in efflux rates in vitro and 60-fold difference in measured in vivo biliary clearance. The predicted biliary clearances from short-term plated rat hepatocytes were within 2-fold of measured in vivo values. As in vitro efflux includes both basolateral and canalicular effluxes, pronounced basolateral efflux may introduce errors in predictions for some compounds. In addition, in vitro rat hepatocyte uptake rates corrected for simultaneous efflux predicted rat in vivo hepatic clearance of the biliary cleared compounds with less than 2-fold error. Short-term plated hepatocytes could thus be used to quantify hepatocyte uptake, metabolism, and efflux of compounds and considerably improve the prediction of hepatic clearance, especially for compounds with a large biliary clearance component. | |
700 | 1 | a Loof, Johan4 aut |
700 | 1 | a Fagerholm, Urban4 aut |
700 | 1 | a Sjogren, Ingemo4 aut |
700 | 1 | a Johansson, Jenny4 aut |
700 | 1 | a Briem, Sveinn4 aut |
700 | 1 | a Hoogstraate, Janet4 aut |
700 | 1 | a Afzelius, Lovisa4 aut |
700 | 1 | a Andersson, Tommy B.4 aut |
710 | 2 | a Uppsala universitetb Institutionen för farmaci4 org |
773 | 0 | t Drug Metabolism And Dispositiond : American Society for Pharmacology & Experimental Therapeutics (ASPET)g 42:3, s. 459-468q 42:3<459-468x 0090-9556x 1521-009X |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-222386 |
856 | 4 8 | u https://doi.org/10.1124/dmd.113.054155 |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:128378718 |
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