PHARMACOLOGY

Kim BROUWER

SITE

Sci Rep. 2022;12:14333. A novel differentiated HuH-7 cell model to examine bile acid metabolism, transport and cholestatic hepatotoxicity. Saran C, Fu D, Ho H, Klein A, Fallon JK, Honkakoski P, Brouwer KLR. PubMed

Clin Pharmacol Ther. 2022;112:573-592. Clinical relevance of hepatic and renal P-gp/BCRP inhibition of drugs: An International Transporter Consortium Perspective. Taskar KS, Yang X, Neuhoff S, Patel M, Yoshida K, Paine MF, Brouwer KLR, Chu X, Sugiyama Y, Cook J, Polli JW, Hanna I, Lai Y, Zamek-Gliszczynski M; ITC. PubMed

Clin Pharmacol Ther. 2022;In press. Considerations for physiologically based modeling in liver disease: From Nonalcoholic Fatty Liver (NAFL) to Nonalcoholic Steatohepatitis (NASH). Murphy WA, Adiwidjaja J, Sjöstedt N, Yang K, Beaudoin JJ, Spires J, Siler SQ, Neuhoff S, Brouwer KLR. PubMed

Clin Pharmacol Ther. 2022;112:461-484.  Regulation of drug transport proteins - From mechanisms to clinical impact; A white paper on behalf of the ITC. Brouwer KLR, Evers R, Hayden E, Hu S, Li CY, Meyer Zu Schwabedissen HE, Neuhoff S, Oswald S, Piquette-Miller M, Saran C, Sjöstedt N, Sprowl J, Stahl SH, Yue W. PubMed

J Pharmacol Exp Ther. 2022;380:114-125. Bile acid-dependent mechanisms of hepatotoxicity associated with Tyrosine Kinase Inhibitors. Saran C, Sundqvist L, Ho H, Niskanen J, Honkakoski P, Brouwer KLR. PubMed

Drug Metab Dispos. 2022;50:58-64. New pharmacokinetic parameters of imaging substrates quantified from rat liver compartments. Pastor CM, Brouwer KL. PubMed

Toxicol Sci. 2021;183:1-13. Analytical and Omics-based advances in the study of drug-induced liver injury. Kralj T, Brouwer KLR, Creek DJ. PubMed

ACS Omega. 2021;6:6708-6713. Rickard BP, Ho H, Tiley JB, Jaspers I, Brouwer KLR. E-Cigarette flavoring chemicals induce cytotoxicity in HepG2 cells. PubMed

J Pharm Sci. 2021;110:404-411. Endogenous Coproporphyrin I and III are altered in Multidrug Resistance associated Protein 2-Deficient (TR) rats. Bezençon J, Saran C, Hussner J, Beaudoin JJ, Zhang Y, Shen H, Fallon JK, Smith PC, Meyer Zu Schwabedissen HE, Brouwer KLR. PubMed

Clin Pharmacol Ther. 2021;109:676-687. Physiologically-Based Pharmacokinetic (PBPK) model of Morphine and Morphine-3-Glucuronide in Nonalcoholic Steatohepatitis (NASH). Sjöstedt N, Neuhoff S, Brouwer KLR. PubMed

Clin Pharmacol Ther. 2021;109:433-442. Quantitative systems toxicology modeling predicts that reduced biliary efflux contributes to Tolvaptan hepatotoxicity. Beaudoin JJ, Brock WJ, Watkins PB, Brouwer KLR. PubMed

Pharm Pharm Sci. 2019;22:567-575. Probe cocktail to assess transporter function in Sandwich-Cultured Human Hepatocytes. J Guo C, Brouwer KR, Stewart PW, Mosley C, Brouwer KLR. PubMed

J Pharmacol Exp Ther. 2020;373:261-268. Hepatic transporter alterations by Nuclear Receptor Agonist T0901317 in Sandwich-Cultured Human Hepatocytes: Proteomic analysis and PBPK Modeling to evaluate Drug-Drug Interaction risk. Ito K, Sjöstedt N, Malinen MM, Guo C, Brouwer KLR. PubMed

Pharmacol Ther. 2020;211:107542. Novel insights into the organic solute transporter alpha/beta, OSTα/β: From the bench to the bedside. Beaudoin JJ, Brouwer KLR, Malinen MM. PubMed

Toxicol Sci. 2020:176:34-35. Role of Organic Solute Transporter Alpha/Beta in hepatotoxic bile acid transport and Drug Interactions. Beaudoin JJ, Bezençon J, Sjöstedt N, Fallon JK, Brouwer KLR. PubMed

Clin Pharmacol Ther. 2021;109:55-64. Intestinal P-gp and putative hepatic OATP1B induction: ITC perspective on drug development implications. Zamek-Gliszczynski MJ, Patel M, Yang X, Lutz JD, Chu X, Brouwer KLR, Lai Y, Lee CA, Neuhoff S, Paine MF, Sugiyama Y, Taskar KS, Galetin A. PubMed

Drug Metab Dispos2020;48:116-122. Mechanistic modeling of the hepatic disposition of Estradiol-17β-Glucuronide in Sandwich-Cultured Human Hepatocytes. Ito K, Sjostedt N, Brouwer KLR. PubMed

Drug Metab Dispos. 2019;47:1222-1230. Optimization of canalicular ABC Transporter function in HuH-7 cells by modification of culture conditions. Kang HE, Malinen MM, Saran C, Honkakoski P, Brouwer KLR. PubMed

Toxicol Sci. 2019;171:431-442. Novel mechanisms of Valproate hepatotoxicity: Impaired Mrp2 trafficking and hepatocyte depolarization. Fu D, Cardona P, Ho H, Watkins PB, Brouwer KLR. PubMed

Mol Pharmacol. 2019;96:158-167. Severe hepatotoxicity of Mithramycin therapy caused by altered expression of hepatocellular bile transporters. Sissung TM, Huang PA, Hauke RJ, McCrea EM, Peer CJ, Barbier RH, Strope JD, Ley AM, Zhang M, Hong JA, Venzon D, Jackson JP, Brouwer KR, Grohar P, Glod J, Widemann BC, Heller T, Schrump DS, Figg WD. PubMed

Drug Metab Dispos. 2019;47:899-906. Altered expression and function of hepatic transporters in a rodent model of Polycystic Kidney Disease. Bezencon J, Beaudoin JJ, Ito K, Fu D, Roth SE, Brock WJ, Brouwer KL. PubMed

J Perinatol. 2019;39:1213-1218. Cefazolin pharmacokinetics in premature infants. Balevic SJ, Smith PB, Testoni D, Wu H, Brouwer KLR, Zimmerman KO, Rivera-Chaparro ND, Benjamin DK, Cohen-Wolkowiez M. PubMed

J Pharm Sci. 2019;108:2484-2489. Increased expression of renal drug transporters in a mouse model of familial Alzheimer's disease. Pan Y, Omori K, Ali I, Tachikawa M, Terasaki T, Brouwer KLR, Nicolazzo JA. PubMed

Eur J Pharm Sci. 2019;130:186-195. Protein expression and function of organic anion transporters in short-term and long-term cultures of Huh7 human hepatoma cells. Malinen MM, Ito K, Kang HE, Honkakoski P, Brouwer KLR. PubMed   

Mol Pharm. 2019;16:1406-1411. Effect of a common genetic variant (p.V444A) in the Bile Salt Export Pump on the inhibition of Bile Acid transport by cholestatic medications. Ali I, Khalid S, Stieger B, Brouwer KLR. PubMed

Drug Metab Dispos. 2019;47:283-294. Continuum of host-gut microbial co-metabolism: Host CYP3A4/3A7 are responsible for tertiary oxidations of Deoxycholate Species. Zhang J, Gao LZ, Chen YJ, Zhu PP, Yin SS, Su MM, Ni Y, Miao J, Wu WL, Chen H, Brouwer KLR, Liu CX, Xu L, Jia W, Lan K. PubMed

Drug Metab Dispos. 2019;47:155-163. Altered hepatobiliary disposition of Tolvaptan and selected Tolvaptan metabolites in a rodent model of Polycystic Kidney Disease. Beaudoin JJ, Bezençon J, Cao Y, Mizuno K, Roth SE, Brock WJ, Brouwer KLR. PubMed

Mol Pharm. 2019;16:238-246. Novel in vitro method reveals drugs that inhibit Solute Transporter Alpha/Beta (OSTα/β). PubMed

Clin Pharmacol Ther. 2019;105:1071-1073. A challenge for clinical pharmacologists: How can we measure scientific impact of publications in drug development and in regulatory decision making? Schmith VD, Reynolds KS, Brouwer KLR, Vicini P. PubMed

Clin Pharmacol Ther. 2018;104:749-756. 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, Brouwer KLR. PubMed

Clin Pharmacol Ther. 2018;104:916-932. Can Bile Salt Export Pump inhibition testing in drug discovery and development reduce liver injury risk? An International Transporter Consortium perspective. Kenna JG, Taskar KS, Battista C, Bourdet DL, Brouwer KLR, Brouwer KR, Dai D, Funk C, Hafey MJ, Lai Y, Maher J, Pak YA, Pedersen JM, Polli JW, Rodrigues AD, Watkins PB, Yang K, Yucha RW; International Transporter Consortium. PubMed

Mol Pharm. 2018;15:4073-4083. Altered expression of small intestinal drug transporters and hepatic metabolic enzymes in a mouse model of familial Alzheimer's disease. Pan Y, Omori K, Ali I, Tachikawa M, Terasaki T, Brouwer KLR, Nicolazzo JA. PubMed

Clin Pharmacol Ther. 2018;104:865-889. Advancing predictions of tissue and intracellular drug concentrations using in vitro, imaging and Physiologically Based Pharmacokinetic Modeling approaches. Guo Y, Chu X, Parrott NJ, Brouwer KLR, Hsu V, Nagar S, Matsson P, Sharma P, Snoeys J, Sugiyama Y, Tatosian D, Unadkat JD, Huang SM, Galetin A; International Transporter Consortium. PubMed

CPT Pharmacometrics Syst Pharmacol. 2018;7:629-637. Physiologically Based Pharmacokinetic approach to determine dosing on extracorporeal life support: Fluconazole in children on ECMO. Watt KM, Cohen-Wolkowiez M, Barrett JS, Sevestre M, Zhao P, Brouwer KLR, Edginton AN. PubMed

Clin Pharmacol Ther. 2018;104:900-915. Disease-associated changes in drug transporters may impact the pharmacokinetics and/or toxicity of drugs: A white paper from the International Transporter Consortium. Evers R, Piquette-Miller M, Polli JW, Russel FGM, Sprowl JA, Tohyama K, Ware JA, de Wildt SN, Xie W, Brouwer KLR; International Transporter Consortium. PubMed

J Pharmacol Exp Ther. 2018;365:413-421. Farnesoid X receptor agonists Obeticholic Acid and Chenodeoxycholic Acid increase bile acid efflux in Sandwich-Cultured Human Hepatocytes: Functional evidence and mechanisms. Guo C, LaCerte C, Edwards JE, Brouwer KR, Brouwer KLR. PubMed

PLoS One. 2018 May 17;13:e0197213. A multi-center preclinical study of gadoxetate DCE-MRI in rats as a biomarker of drug induced inhibition of liver transporter function. Karageorgis A, Lenhard SC, Yerby B, Forsgren MF, Liachenko S, Johansson E, Pilling MA, Peterson RA, Yang X, Williams DP, Ungersma SE, Morgan RE, Brouwer KLR, Jucker BM, Hockings PD. PubMed

Am J Physiol Gastrointest Liver Physiol. 2018;314:G597-G609. Organic solute transporter OSTα/β is overexpressed in nonalcoholic steatohepatitis and modulated by drugs associated with liver injury. Malinen MM, Ali I, Bezençon J, Beaudoin JJ, Brouwer KLR. PubMed

Eur J Pharm Sci. 2017;103:52-59. Identification of novel MRP3 inhibitors based on computational models and validation using an in vitro membrane vesicle assay. Ali I1, Welch MA2, Lu Y1, Swaan PW2, Brouwer KLR3. PubMed

CPT Pharmacometrics Syst Pharmacol. 2017;6:331-339. Population pharmacokinetics of morphine in patients with Nonalcoholic Steatohepatitis (NASH) and healthy adults. Pierre V, Johnston CK, Ferslew BC, Brouwer K, Gonzalez D. PubMed

J Pharm Sci. 2017;106:2282-2294. Effect of Liver Disease on Hepatic Transporter Expression and Function. Thakkar N, Slizgi JR, Brouwer KLR. PubMed

Toxicol Sci. 2017;155:61-74. 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. PubMed

J Pharmacol Exp Ther. 2016;358:324-33.,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, Brouwer KL. PubMed

J Pharm Sci. 2016;105:443-59. 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 KL. PubMed

Toxicol Sci. 2016;149:237-50. 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. PubMed

Dig Dis Sci. 2015;60:3318-28.  Altered bile acid metabolome in patients with nonalcoholic steatohepatitis. Ferslew BC, Xie G, Johnston CK, Su M, Stewart PW, Jia W, Brouwer KL, Sidney Barritt A. PubMed

Clin Pharmacol Ther. 2015;98:266-87. 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. PubMed

Drug Metab Dispos. 2015;43:725-34. 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. PubMed

Drug Metab Dispos. 2015;43:725-34. doi: 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. PubMed

J Pharmacol Exp Ther. 2015;353:415-23. 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. PubMed

Clin Pharmacol Ther. 2015;97:419-27. 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. PubMed

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