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Organic Solute Transporter OSTα/ß is Over-Expressed in Nonalcoholic Steatohepatitis and Modulated by Drugs Associated with Liver Injury.

Malinen MM, Ali I, Bezençon J, Beaudoin JJ, Brouwer KLR.

Am J Physiol Gastrointest Liver Physiol. 2018 Feb 8. doi: 10.1152/ajpgi.00310.2017. [Epub ahead of print]


Transporter-Mediated Alterations in Patients With NASH Increase Systemic and Hepatic Exposure to an OATP and MRP2 Substrate.

Ali I, Slizgi JR, Kaullen JD, Ivanovic M, Niemi M, Stewart PW, Barritt AS 4th, Brouwer KLR.

Clin Pharmacol Ther. 2017 Dec 22. doi: 10.1002/cpt.997. [Epub ahead of print]


In vitro to in vivo extrapolation for high throughput prioritization and decision making.

Bell SM, Chang X, Wambaugh JF, Allen DG, Bartels M, Brouwer KLR, Casey WM, Choksi N, Ferguson SS, Fraczkiewicz G, Jarabek AM, Ke A, Lumen A, Lynn SG, Paini A, Price PS, Ring C, Simon TW, Sipes NS, Sprankle CS, Strickland J, Troutman J, Wetmore BA, Kleinstreuer NC.

Toxicol In Vitro. 2018 Mar;47:213-227. doi: 10.1016/j.tiv.2017.11.016. Epub 2017 Dec 5. Review.


Antifungal Extraction by the Extracorporeal Membrane Oxygenation Circuit.

Watt KM, Cohen-Wolkowiez M, Williams DC, Bonadonna DK, Cheifetz IM, Thakker D, Benjamin DK Jr, Brouwer KLR.

J Extra Corpor Technol. 2017 Sep;49(3):150-159.


Precision Dosing: Public Health Need, Proposed Framework, and Anticipated Impact.

Gonzalez D, Rao GG, Bailey SC, Brouwer KLR, Cao Y, Crona DJ, Kashuba ADM, Lee CR, Morbitzer K, Patterson JH, Wiltshire T, Easter J, Savage SW, Powell JR.

Clin Transl Sci. 2017 Nov;10(6):443-454. doi: 10.1111/cts.12490. Epub 2017 Aug 10. Review. No abstract available.


Effect of Liver Disease on Hepatic Transporter Expression and Function.

Thakkar N, Slizgi JR, Brouwer KLR.

J Pharm Sci. 2017 Sep;106(9):2282-2294. doi: 10.1016/j.xphs.2017.04.053. Epub 2017 Apr 30. Review.


Prediction of Hepatic Efflux Transporter-Mediated Drug Interactions: When Is it Optimal to Measure Intracellular Unbound Fraction of Inhibitors?

Guo C, Yang K, Liao M, Xia CQ, Brouwer KR, Brouwer KLR.

J Pharm Sci. 2017 Sep;106(9):2401-2406. doi: 10.1016/j.xphs.2017.04.054. Epub 2017 Apr 30.


Identification of novel MRP3 inhibitors based on computational models and validation using an in vitro membrane vesicle assay.

Ali I, Welch MA, Lu Y, Swaan PW, Brouwer KLR.

Eur J Pharm Sci. 2017 May 30;103:52-59. doi: 10.1016/j.ejps.2017.02.011. Epub 2017 Feb 24.


Pharmacokinetics and Safety of Micafungin in Infants Supported With Extracorporeal Membrane Oxygenation.

Autmizguine J, Hornik CP, Benjamin DK Jr, Brouwer KL, Hupp SR, Cohen-Wolkowiez M, Watt KM.

Pediatr Infect Dis J. 2016 Nov;35(11):1204-1210.


Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors.

Woodhead JL, Brock WJ, Roth SE, Shoaf SE, Brouwer KL, Church R, Grammatopoulos TN, Stiles L, Siler SQ, Howell BA, Mosedale M, Watkins PB, Shoda LK.

Toxicol Sci. 2017 Jan;155(1):61-74. doi: 10.1093/toxsci/kfw193. Epub 2016 Sep 21.


Characterization of the Cytochrome P450 epoxyeicosanoid pathway in non-alcoholic steatohepatitis.

Wells MA, Vendrov KC, Edin ML, Ferslew BC, Zha W, Nguyen BK, Church RJ, Lih FB, DeGraff LM, Brouwer KL, Barritt AS 4th, Zeldin DC, Lee CR.

Prostaglandins Other Lipid Mediat. 2016 Sep;125:19-29. doi: 10.1016/j.prostaglandins.2016.07.002. Epub 2016 Jul 9.


Key Role for the 12-Hydroxy Group in the Negative Ion Fragmentation of Unconjugated C24 Bile Acids.

Lan K, Su M, Xie G, Ferslew BC, Brouwer KL, Rajani C, Liu C, Jia W.

Anal Chem. 2016 Jul 19;88(14):7041-8. doi: 10.1021/acs.analchem.6b00573. Epub 2016 Jun 30.


Prediction of Altered Bile Acid Disposition Due to Inhibition of Multiple Transporters: An Integrated Approach Using Sandwich-Cultured Hepatocytes, Mechanistic Modeling, and Simulation.

Guo C, Yang K, Brouwer KR, St Claire RL 3rd, Brouwer KL.

J Pharmacol Exp Ther. 2016 Aug;358(2):324-33. doi: 10.1124/jpet.116.231928. Epub 2016 May 27.


Hepatocellular Disposition and Transporter Interactions with Tolvaptan and Metabolites in Sandwich-Cultured Human Hepatocytes.

Lu Y, Slizgi JR, Brouwer KR, Claire RL, Freeman KM, Pan M, Brock WJ, Brouwer KL.

Drug Metab Dispos. 2016 Mar 24. pii: dmd.115.067629. [Epub ahead of print]


Sandwich-Cultured Hepatocytes as a Tool to Study Drug Disposition and Drug-Induced Liver Injury.

Yang K, Guo C, Woodhead JL, St Claire RL 3rd, Watkins PB, Siler SQ, Howell BA, Brouwer KLR.

J Pharm Sci. 2016 Feb;105(2):443-459. doi: 10.1016/j.xphs.2015.11.008. Review.


Inhibition of Human Hepatic Bile Acid Transporters by Tolvaptan and Metabolites: Contributing Factors to Drug-Induced Liver Injury?

Slizgi JR, Lu Y, Brouwer KR, St Claire RL, Freeman KM, Pan M, Brock WJ, Brouwer KL.

Toxicol Sci. 2016 Jan;149(1):237-50. doi: 10.1093/toxsci/kfv231. Epub 2015 Oct 26.


Altered Bile Acid Metabolome in Patients with Nonalcoholic Steatohepatitis.

Ferslew BC, Xie G, Johnston CK, Su M, Stewart PW, Jia W, Brouwer KL, Barritt AS 4th.

Dig Dis Sci. 2015 Nov;60(11):3318-28. doi: 10.1007/s10620-015-3776-8. Epub 2015 Jul 3.


Human Ontogeny of Drug Transporters: Review and Recommendations of the Pediatric Transporter Working Group.

Brouwer KL, Aleksunes LM, Brandys B, Giacoia GP, Knipp G, Lukacova V, Meibohm B, Nigam SK, Rieder M, de Wildt SN; Pediatric Transporter Working Group.

Clin Pharmacol Ther. 2015 Sep;98(3):266-87. doi: 10.1002/cpt.176. Review.


Fluconazole population pharmacokinetics and dosing for prevention and treatment of invasive Candidiasis in children supported with extracorporeal membrane oxygenation.

Watt KM, Gonzalez D, Benjamin DK Jr, Brouwer KL, Wade KC, Capparelli E, Barrett J, Cohen-Wolkowiez M.

Antimicrob Agents Chemother. 2015 Jul;59(7):3935-43. doi: 10.1128/AAC.00102-15. Epub 2015 Apr 20.


Toward predicting drug-induced liver injury: parallel computational approaches to identify multidrug resistance protein 4 and bile salt export pump inhibitors.

Welch MA, Köck K, Urban TJ, Brouwer KL, Swaan PW.

Drug Metab Dispos. 2015 May;43(5):725-34. doi: 10.1124/dmd.114.062539. Epub 2015 Mar 3.


Species differences in hepatobiliary disposition of taurocholic acid in human and rat sandwich-cultured hepatocytes: implications for drug-induced liver injury.

Yang K, Pfeifer ND, Köck K, Brouwer KL.

J Pharmacol Exp Ther. 2015 May;353(2):415-23. doi: 10.1124/jpet.114.221564. Epub 2015 Feb 23.


Altered morphine glucuronide and bile acid disposition in patients with nonalcoholic steatohepatitis.

Ferslew BC, Johnston CK, Tsakalozou E, Bridges AS, Paine MF, Jia W, Stewart PW, Barritt AS 4th, Brouwer KL.

Clin Pharmacol Ther. 2015 Apr;97(4):419-27. doi: 10.1002/cpt.66. Epub 2015 Mar 15.


Exploring BSEP inhibition-mediated toxicity with a mechanistic model of drug-induced liver injury.

Woodhead JL, Yang K, Siler SQ, Watkins PB, Brouwer KL, Barton HA, Howell BA.

Front Pharmacol. 2014 Nov 7;5:240. doi: 10.3389/fphar.2014.00240. eCollection 2014.


Novel mechanism of impaired function of organic anion-transporting polypeptide 1B3 in human hepatocytes: post-translational regulation of OATP1B3 by protein kinase C activation.

Powell J, Farasyn T, Köck K, Meng X, Pahwa S, Brouwer KL, Yue W.

Drug Metab Dispos. 2014 Nov;42(11):1964-70. doi: 10.1124/dmd.114.056945. Epub 2014 Sep 8.


Systems pharmacology modeling predicts delayed presentation and species differences in bile acid-mediated troglitazone hepatotoxicity.

Yang K, Woodhead JL, Watkins PB, Howell BA, Brouwer KL.

Clin Pharmacol Ther. 2014 Nov;96(5):589-98. doi: 10.1038/clpt.2014.158. Epub 2014 Jul 28.


Medication use and medical comorbidity in patients with chronic hepatitis C from a US commercial claims database: high utilization of drugs with interaction potential.

Lauffenburger JC, Mayer CL, Hawke RL, Brouwer KL, Fried MW, Farley JF.

Eur J Gastroenterol Hepatol. 2014 Oct;26(10):1073-82. doi: 10.1097/MEG.0000000000000152.


Mechanistic Modeling Reveals the Critical Knowledge Gaps in Bile Acid-Mediated DILI.

Woodhead JL, Yang K, Brouwer KL, Siler SQ, Stahl SH, Ambroso JL, Baker D, Watkins PB, Howell BA.

CPT Pharmacometrics Syst Pharmacol. 2014 Jul 9;3:e123. doi: 10.1038/psp.2014.21.


Role of multidrug resistance-associated protein 4 in the basolateral efflux of hepatically derived enalaprilat.

Ferslew BC, Köck K, Bridges AS, Brouwer KL.

Drug Metab Dispos. 2014 Sep;42(9):1567-74. doi: 10.1124/dmd.114.057554. Epub 2014 Jun 23.


Population pharmacokinetics of azithromycin in whole blood, peripheral blood mononuclear cells, and polymorphonuclear cells in healthy adults.

Sampson MR, Dumitrescu TP, Brouwer KL, Schmith VD.

CPT Pharmacometrics Syst Pharmacol. 2014 Mar 5;3:e103. doi: 10.1038/psp.2013.80.


Role of hepatic efflux transporters in regulating systemic and hepatocyte exposure to xenobiotics.

Pfeifer ND, Hardwick RN, Brouwer KL.

Annu Rev Pharmacol Toxicol. 2014;54:509-35. doi: 10.1146/annurev-pharmtox-011613-140021. Epub 2013 Oct 23. Review.


Risk factors for development of cholestatic drug-induced liver injury: inhibition of hepatic basolateral bile acid transporters multidrug resistance-associated proteins 3 and 4.

Köck K, Ferslew BC, Netterberg I, Yang K, Urban TJ, Swaan PW, Stewart PW, Brouwer KL.

Drug Metab Dispos. 2014 Apr;42(4):665-74. doi: 10.1124/dmd.113.054304. Epub 2013 Oct 23.


Hepatic basolateral efflux contributes significantly to rosuvastatin disposition II: characterization of hepatic elimination by basolateral, biliary, and metabolic clearance pathways in rat isolated perfused liver.

Pfeifer ND, Bridges AS, Ferslew BC, Hardwick RN, Brouwer KL.

J Pharmacol Exp Ther. 2013 Dec;347(3):737-45. doi: 10.1124/jpet.113.208314. Epub 2013 Sep 30.


In vivo alterations in drug metabolism and transport pathways in patients with chronic kidney diseases.

Joy MS, Frye RF, Nolin TD, Roberts BV, La MK, Wang J, Brouwer KL, Dooley MA, Falk RJ.

Pharmacotherapy. 2014 Feb;34(2):114-22. doi: 10.1002/phar.1347. Epub 2013 Sep 6.


Determination of intracellular unbound concentrations and subcellular localization of drugs in rat sandwich-cultured hepatocytes compared with liver tissue.

Pfeifer ND, Harris KB, Yan GZ, Brouwer KL.

Drug Metab Dispos. 2013 Nov;41(11):1949-56. doi: 10.1124/dmd.113.052134. Epub 2013 Aug 29.


Effect of Ritonavir on (99m)Technetium-Mebrofenin Disposition in Humans: A Semi-PBPK Modeling and In Vitro Approach to Predict Transporter-Mediated DDIs.

Pfeifer ND, Goss SL, Swift B, Ghibellini G, Ivanovic M, Heizer WD, Gangarosa LM, Brouwer KL.

CPT Pharmacometrics Syst Pharmacol. 2013 Jan 2;2:e20. doi: 10.1038/psp.2012.21.


Relative bioavailability of tolvaptan administered via nasogastric tube and tolvaptan tablets swallowed intact.

McNeely EB, Talameh JA, Adams KF Jr, Hull JH, Simmons B, Henry J, Brouwer KL, Patterson JH.

Am J Health Syst Pharm. 2013 Jul 15;70(14):1230-7. doi: 10.2146/ajhp120543.


Organic cation transporter 1 (OCT1/mOct1) is localized in the apical membrane of Caco-2 cell monolayers and enterocytes.

Han TK, Everett RS, Proctor WR, Ng CM, Costales CL, Brouwer KL, Thakker DR.

Mol Pharmacol. 2013 Aug;84(2):182-9. doi: 10.1124/mol.112.084517. Epub 2013 May 16.


An updated review on drug-induced cholestasis: mechanisms and investigation of physicochemical properties and pharmacokinetic parameters.

Yang K, Köck K, Sedykh A, Tropsha A, Brouwer KL.

J Pharm Sci. 2013 Sep;102(9):3037-57. doi: 10.1002/jps.23584. Epub 2013 May 7. Review.


Development of a population pharmacokinetic model to describe azithromycin whole-blood and plasma concentrations over time in healthy subjects.

Pene Dumitrescu T, Anic-Milic T, Oreskovic K, Padovan J, Brouwer KL, Zuo P, Schmith VD.

Antimicrob Agents Chemother. 2013 Jul;57(7):3194-201. doi: 10.1128/AAC.02430-12. Epub 2013 Apr 29.


Intracellular drug concentrations and transporters: measurement, modeling, and implications for the liver.

Chu X, Korzekwa K, Elsby R, Fenner K, Galetin A, Lai Y, Matsson P, Moss A, Nagar S, Rosania GR, Bai JP, Polli JW, Sugiyama Y, Brouwer KL; International Transporter Consortium.

Clin Pharmacol Ther. 2013 Jul;94(1):126-41. doi: 10.1038/clpt.2013.78. Epub 2013 Apr 10. Review.


In vitro methods to support transporter evaluation in drug discovery and development.

Brouwer KL, Keppler D, Hoffmaster KA, Bow DA, Cheng Y, Lai Y, Palm JE, Stieger B, Evers R; International Transporter Consortium.

Clin Pharmacol Ther. 2013 Jul;94(1):95-112. doi: 10.1038/clpt.2013.81. Epub 2013 Apr 10. Review. Erratum in: Clin Pharmacol Ther. 2013 Sep;94(3):412.


Sorafenib hepatobiliary disposition: mechanisms of hepatic uptake and disposition of generated metabolites.

Swift B, Nebot N, Lee JK, Han T, Proctor WR, Thakker DR, Lang D, Radtke M, Gnoth MJ, Brouwer KL.

Drug Metab Dispos. 2013 Jun;41(6):1179-86. doi: 10.1124/dmd.112.048181. Epub 2013 Mar 12.


Interaction of silymarin flavonolignans with organic anion-transporting polypeptides.

Köck K, Xie Y, Hawke RL, Oberlies NH, Brouwer KL.

Drug Metab Dispos. 2013 May;41(5):958-65. doi: 10.1124/dmd.112.048272. Epub 2013 Feb 11.


Combination lopinavir and ritonavir alter exogenous and endogenous bile acid disposition in sandwich-cultured rat hepatocytes.

Griffin LM, Watkins PB, Perry CH, St Claire RL 3rd, Brouwer KL.

Drug Metab Dispos. 2013 Jan;41(1):188-96. doi: 10.1124/dmd.112.047225. Epub 2012 Oct 22.


A perspective on efflux transport proteins in the liver.

Köck K, Brouwer KL.

Clin Pharmacol Ther. 2012 Nov;92(5):599-612. doi: 10.1038/clpt.2012.79. Epub 2012 Sep 5. Review.


Pharmacokinetics and safety of fluconazole in young infants supported with extracorporeal membrane oxygenation.

Watt KM, Benjamin DK Jr, Cheifetz IM, Moorthy G, Wade KC, Smith PB, Brouwer KL, Capparelli EV, Cohen-Wolkowiez M.

Pediatr Infect Dis J. 2012 Oct;31(10):1042-7. doi: 10.1097/INF.0b013e31825d3091.

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