Drug-metabolising enzyme expression

  • Drug Metab Dispos. 2018;46:943-952. Abundance of phase 1 and 2 drug-metabolizing enzymes in alcoholic and hepatitis C cirrhotic livers: a quantitative targeted proteomics study. Prasad B, Bhatt DK, Johnson K, Chapa R, Chu X, Salphati L, Xiao G, Lee C, Hop CECA, Mathias A, Lai Y, Liao M, Humphreys WG, Kumer SC, Unadkat JD. PubMed

Transporter expression and lobular zonation

  • Drug Metab Dispos. 2018;46:610-618. Liver zonation index of drug transporter and metabolizing enzyme protein expressions in mouse liver acinus. Tachikawa M, Sumiyoshiya Y, Saigusa D, Sasaki K, Watanabe M, Uchida Y, Terasaki T. This study clarifies the zonated drug distributions in mouse liver based on the protein expression of transporters and metabolizing enzymes in periportal (PP) and pericentral (PC) areas of mouse lobules. PubMed

Transporter-enzyme interplay

  • Drug Metab Dispos. 2018; 46(5):680-691. Sandwich-cultured hepatocytes for mechanistic understanding of hepatic disposition of parent drugs and metabolites by transporter-enzyme interplay. Matsunaga N, Fukuchi Y, Imawaka H, Tamai I. The authors review the utility and applicability of sandwich-cultured hepatocytes for mechanistic understanding of hepatic disposition of both parent drugs and metabolites. PubMed

ABC transporters and cancer

  • Nat Rev Cancer. 2018; in press. Revisiting the role of ABC transporters in multidrug-resistant cancer. Robey RW, Pluchino KM, Hall MD, Fojo AT, Bates SE, Gottesman MM. PubMed

Drug-drug interactions

  • Drug Metab Dispos. 2018;46:697-703. MRP2 inhibition by HIV protease inhibitors in rat and human hepatocytes: a quantitative confocal microscopy study. Holmstock N, Oorts M1, Snoeys J, Annaert P. The authors used confocal microscopy to investigate the inhibitory effect of all marketed HIV protease inhibitors on MRP2 by visualizing the biliary accumulation of the fluorescent substrate 5(6)-carboxy-2',7'-dichlorofluorescein (CDF). PubMed
  • Drug Metab Dispos. 2018,46:704-718. Intravital multiphoton microscopy with fluorescent bile salts in rats as an in vivo biomarker for hepatobiliary transport inhibition. Ryan J, Morgan RE, Chen Y, Volak L, Dunn RT, Dunn KW. The study uses quantitative intravital microscopy to identify the dose-dependent effects of two BSEP/Bsep inhibitors on the hepatocellular transport of fluorescent bile salts in rats. PubMed
  • Drug Metab Dispos. 2018;46:924-933. Quantitative analysis of complex drug-drug interactions between Cerivastatin and metabolism/transport inhibitors using physiologically based pharmacokinetic modeling. Yao Y, Toshimoto K, Kim SJ, Yoshikado T, Sugiyama Y. PubMed
  • Basic Clin Pharmacol Toxicol. 2018, in press. Interaction of Sulfonylureas with liver uptake transporters OATP1B1 and OATP1B3. Chen Y, Chen L, Zhang H, Huang S, Xiong Y, Xia C. PubMed
  • Drug Metab Dispos. 2018;46:835-845. Risk of clinically relevant pharmacokinetic-based drug-drug interactions with drugs approved by the U.S. Food and Drug Administration Between 2013 and 2016. Yu J, Zhou Z, Tay-Sontheimer J, Levy RH, Ragueneau-Majlessi I. A total of 103 drugs (including 14 combination drugs) were approved by the U.S. Food and Drug Administration from 2013 to 2016. Pharmacokinetic-based drug interaction profiles were analyzed using the University of Washington Drug Interaction Database, and the clinical relevance of these observations was characterized based on information from new drug application reviews. PubMed
  • J Pharmacol Exp Ther. 2018;365:519-525. In vitro assessment of pharmacokinetic drug-drug interactions of direct oral anticoagulants: type 5-phosphodiesterase inhibitors are inhibitors of Rivaroxaban and Apixaban efflux by P-Glycoprotein. Margelidon-Cozzolino V, Hodin S, Jacqueroux E, Delézay O, Bertoletti L, Delavenne X. PubMed
  • J Pharmacol Exp Ther. 2018;365:688-699. In vitro-in vivo extrapolation of OATP1B-mediated drug-drug interactions in Cynomolgus monkey. Ufuk A, Kosa RE, Gao H, Bi YA, Modi S, Gates D, Rodrigues AD, Tremaine LM, Varma MVS, Houston JB, Galetin A. PubMed

Transporter regulation

  • Drug Metab Dispos. 2018;46:503-513. Physiological regulation of drug metabolism and transport: pregnancy, microbiome, inflammation, infection, and fasting. Morgan ET, Dempsey JL, Mimche SM, Lamb TJ, Kulkarni S, Cui JY, Jeong H, Slitt AL. This article is a report of the symposium "Physiological Regulation of Drug Metabolism and Transport" sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 2017 meeting in Chicago, IL. PubMed
  • J Pharmacol Exp Ther. 2018;365:237-248. Simultaneous assessment of clearance, metabolism, induction, and drug-drug interaction potential using a long-term in vitro liver model for a novel hepatitis B virus inhibitor. Kratochwil NA, Triyatni M, Mueller MB, Klammers F, Leonard B, Turley D, Schmaler J, Ekiciler A, Molitor B, Walter I, Gonsard PA, Tournillac CA, Durrwell A, Marschmann M, Jones R, Ullah M, Boess F, Ottaviani G, Jin Y, Parrott NJ, Fowler S. PubMed
  • Curr Med Chem. 2018, in press. Modulation of hepatic MRP3/ABCC3 by xenobiotics and pathophysiological conditions: role in drug pharmacokinetics. Ghanem CI, Manautou JE. This review summarises the changes in expression and regulation of the basolateral hepatic transporter MPR3/ABCC3 by xenobiotics and various pathophysiological conditions. 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
  • Biochim Biophys Acta. 2018;1864:1072-1085. Mechanisms of canalicular transporter endocytosis in the cholestatic rat liver. Miszczuk GS, Barosso IR, Larocca MC, Marrone J, Marinelli RA, Boaglio AC, Sánchez Pozzi EJ, Roma MG, Crocenzi FA. PubMed
  • Oncotarget. 2017;8:115667-115680. Loss of organic cation transporter 3 (Oct3) leads to enhanced proliferation and hepatocarcinogenesis. Vollmar J, Lautem A, Closs E, Schuppan D, Kim YO, Grimm D, Marquardt JU, Fuchs P, Straub BK, Schad A, Gründemann D, Schattenberg JM, Gehrke N, Wörns MA, Baumgart J, Galle PR, Zimmermann T. PubMed

Regulation of bile acid transport

  • J Pharmacol Exp Ther. 2018;365:413-421. FXR 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
  • Hepatology. 2018;67:1531-1545. Zebrafish abcb11b mutant reveals strategies to restore bile excretion impaired by bile salt export pump deficiency. Ellis JL, Bove KE, Schuetz EG, Leino D, Valencia CA, Schuetz JD, Miethke A, Yin C1. The study suggests that rapamycin rescues BSEP-deficient phenotypes by prompting alternative transporters to excrete bile salts; multidrug resistance protein 1 is a candidate for such an alternative transporter. PubMed

Drug transport

  • Drug Metab Dispos. 2018;46:652-657. Organic anion transporting polypeptide 1a4 is responsible for the hepatic uptake of cardiac glycosides in mice. Takano J, Maeda K, Kusuhara H, Sugiyama Y. PubMed

Transporters and imaging

  • Nucl Med Biol. 2018;60:29-36. A new method measuring the interaction of radiotracers with the human P-glycoprotein (P-gp) transporter. Vraka C, Dumanic M, Racz T, Pichler F, Philippe C, Balber T, Klebermass EM, Wagner KH, Hacker M, Wadsak W, Mitterhauser M. PubMed
  • Pharmacol Ther. 2018; in press. Imaging techniques to study drug transporter function in vivo. Tournier N, Stieger B, Langer O. PubMed
  • J Nucl Med. 2018; in press. P-glycoprotein (ABCB1) inhibits the influx and increases the efflux of 11C-metoclopramide across the blood-brain barrier: a PET study on non-human primates. Auvity S, Caillé F, Marie S, Wimberley C, Bauer M, Langer O, Buvat I, Goutal S, Tournier N. PubMed
  • Nucl Med Biol. 2018;61:56-62. N-(4-[18F]fluorobenzyl)cholylglycine, a novel tracer for PET of enterohepatic circulation of bile acids: Radiosynthesis and proof-of-concept studies in rats. Frisch K, Stimson DHR, Venkatachalam T, Pierens GK, Keiding S, Reutens D, Bhalla R. PubMed
  • Am J Nucl Med Mol Imaging. 2018;8:73-85. Quantitative PET of liver functions. Keiding S, Sørensen M, Frisch K, Gormsen LC, Munk OL. PubMed