ELIZA cgi-bash version rev. 1.91
- Medical English LInking keywords finder for the PubMed Zipped Archive (ELIZA) -

return kwic search for showed out of >500 occurrences
663834 occurrences (No.9 in the rank) during 5 years in the PubMed. [cache]
29) Results showed that NMP of porcine livers is a reliable model to study OATP-mediated DDI.
--- ABSTRACT ---
PMID:34330719 DOI:10.1124/dmd.121.000521
2021 Drug metabolism and disposition: the biological fate of chemicals
* Evaluation of Normothermic Machine Perfusion of Porcine Livers as a Novel Preclinical Model to Predict Biliary Clearance and Transporter-Mediated Drug-Drug Interactions Using Statins.
- There is a lack of translational preclinical models that can predict hepatic handling of drugs. In this study, we aimed to evaluate the applicability of normothermic machine perfusion (NMP) of porcine livers as a novel ex vivo model to predict hepatic clearance, biliary excretion, and plasma exposure of drugs. For this evaluation, we dosed atorvastatin, pitavastatin, and rosuvastatin as model drugs to porcine livers and studied the effect of common drug-drug interactions (DDIs) on these processes. After 120 minutes of perfusion, 0.104 mg atorvastatin (n = 3), 0.140 mg pitavastatin (n = 5), or 1.4 mg rosuvastatin (n = 4) was administered to the portal vein, which was followed 120 minutes later by a second bolus of the statin coadministered with OATP perpetrator drug rifampicin (67.7 mg). After the first dose, all statins were rapidly cleared from the circulation (hepatic extraction ratio > 0.7) and excreted into the bile. Presence of human-specific atorvastatin metabolites confirmed the metabolic capacity of porcine livers. The predicted biliary clearance of rosuvastatin was found to be closer to the observed biliary clearance. A rank order of the DDI between the various systems upon coadministration with rifampicin could be observed: atorvastatin (AUC ratio 7.2) > rosuvastatin (AUC ratio 3.1) > pitavastatin (AUC ratio 2.6), which is in good agreement with the clinical DDI data. The results from this study demonstrated the applicability of using NMP of porcine livers as a novel preclinical model to study OATP-mediated DDI and its effect on hepatic clearance, biliary excretion, and plasma profile of drugs. SIGNIFICANCE STATEMENT: This study evaluated the use of normothermic machine perfusion (NMP) of porcine livers as a novel preclinical model to study hepatic clearance, biliary excretion, plasma (metabolite) profile of statins, and OATP-mediated DDI. Results showed that NMP of porcine livers is a reliable model to study OATP-mediated DDI. Overall, the rank order of DDI severity indicated in these experiments is in good agreement with clinical data, indicating the potential importance of this new ex vivo model in early drug discovery.
--- ABSTRACT END ---
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[frequency of next (right) word to showed]
(1)197 that (10)5 higher (19)3 moderate (28)2 large
(2)50 a (11)5 significantly (20)3 more (29)2 lower
(3)23 the (12)4 differential (21)3 mostly (30)2 reduced
(4)14 no (13)4 greater (22)3 promising (31)2 remarkable
(5)12 an (14)4 positive (23)2 clinically (32)2 similar
(6)11 significant (15)3 better (24)2 efficacy (33)2 stereoselectivity
(7)6 good (16)3 extensive (25)2 hypersensitivity (34)2 strong
(8)6 high (17)3 how (26)2 impairments
(9)5 elevated (18)3 low (27)2 increased

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--- WordNet output for showed --- Overview of verb show The verb show has 12 senses (first 11 from tagged texts) 1. (136) show, demo, exhibit, present, demonstrate -- (give an exhibition of to an interested audience; "She shows her dogs frequently"; "We will demo the new software in Washington") 2. (63) prove, demonstrate, establish, show, shew -- (establish the validity of something, as by an example, explanation or experiment; "The experiment demonstrated the instability of the compound"; "The mathematician showed the validity of the conjecture") 3. (57) testify, bear witness, prove, evidence, show -- (provide evidence for; "The blood test showed that he was the father"; "Her behavior testified to her incompetence") 4. (43) show -- (make visible or noticeable; "She showed her talent for cooking"; "Show me your etchings, please") 5. (32) picture, depict, render, show -- (show in, or as in, a picture; "This scene depicts country life"; "the face of the child is rendered with much tenderness in this painting") 6. (24) express, show, evince -- (give expression to; "She showed her disappointment") 7. (24) indicate, point, designate, show -- (indicate a place, direction, person, or thing; either spatially or figuratively; "I showed the customer the glove section"; "He pointed to the empty parking space"; "he indicated his opponents") 8. (11) show, show up -- (be or become visible or noticeable; "His good upbringing really shows"; "The dirty side will show") 9. (7) read, register, show, record -- (indicate a certain reading; of gauges and instruments; "The thermometer showed thirteen degrees below zero"; "The gauge read `empty'") 10. (6) show -- (give evidence of, as of records; "The diary shows his distress that evening") 11. (2) usher, show -- (take (someone) to their seats, as in theaters or auditoriums; "The usher showed us to our seats") 12. show -- (finish third or better in a horse or dog race; "he bet $2 on number six to show") --- WordNet end ---