Liver imaging

  • Invest Radiol. 2018;53:563-570. Modeling gadoxetate liver uptake and efflux using dynamic contrast-enhanced Magnetic Resonance Imaging enables preclinical quantification of transporter drug-drug interactions. Georgiou L, Penny J, Nicholls G, Woodhouse N, Blé FX, Naish JH, Hubbard Cristinacce PL. PubMed
  • Drug Metab Dispos. 2018;46:719-728. A clinical quantitative evaluation of hepatobiliary transport of [11C]Dehydropravastatin in humans using Positron Emission Tomography. Kaneko K, Tanaka M, Ishii A, Katayama Y, Nakaoka T, Irie S, Kawahata H, Yamanaga T, Wada Y, Miyake T, Toshimoto K, Maeda K, Cui Y, Enomoto M, Kawamura E, Kawada N, Kawabe J, Shiomi S, Kusuhara H, Sugiyama Y, Watanabe Y. PubMed
  • PLoS One. 2018;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

14C microtracer ADME studies

  • Bioanalysis. 2018;10:321-339. Evaluation of cAMS for 14C microtracer ADME studies: opportunities to change the current drug development paradigm. Lozac'h F, Fahrni S, Maria D, Welte C, Bourquin J, Synal HA, Pearson D, Walles M, Camenisch G. PubMed
  • Drug Metab Dispos. 2017;45:900-907. Comparison of 19F NMR and 14C measurements for the assessment of ADME of BYL719 (Alpelisib) in humans. James AD, Marvalin C, Luneau A, Meissner A, Camenisch G. PubMed

Guidance for regulatory agencies

Transport expression and regulation

  • Pathol Oncol Res. 2018; in press. Immunohistochemical assessment of the expression of biliary transportation proteins MRP2 and MRP3 in hepatocellular carcinoma and in cholangiocarcinoma. Cirqueira CS, Felipe-Silva AS, Wakamatsu A, Marins LV, Rocha EC, de Mello ES, Alves VAF. PubMed
  • Gastroenterology. 2018;in press. Dysregulated bile transporters and impaired tight junctions during chronic liver injury in mice. Pradhan-Sundd T, Vats R, Russell JM, Singh S, Michael AA, Molina L, Kakar S, Cornuet P, Poddar M, Watkins SC, Nejak-Bowen KN, Monga SP, Sundd P. PubMed
  • Mol Pharm. 2018;15:3227-3235. Quantification of hepatic organic anion transport proteins OAT2 and OAT7 in human liver tissue and primary hepatocytes. Vildhede A, Kimoto E, Rodrigues AD, Varma MVS. PubMed
  • J Lipid Res. 2018;in press. Thyroid hormone receptor β1 stimulates ABCB4 to increase biliary phosphatidylcholine excretion in mice. Gautherot J, Claudel T, Cuperus F, Fuchs CD, Falguieres T, Trauner M. PubMed
  • Hepatol Commun. 2018;2:693-702. Age-dependent glycosylation of the sodium taurocholate cotransporter polypeptide: from fetal to adult human livers. Sargiacomo C, El-Kehdy H, Pourcher G, Stieger B, Najimi M, Sokal E. PubMed
  • PLoS Genet. 2018;14:e1007380. Sustained activation of detoxification pathways promotes liver carcinogenesis in response to chronic bile acid-mediated damage. Collino A, Termanini A, Nicoli P, Diaferia G, Polletti S, Recordati C, Castiglioni V, Caruso D, Mitro N, Natoli G, Ghisletti S. PubMed
  • Pharmacol Ther. 2018;in press. Post-translational modifications of transporters. Czuba LC, Hillgren KM, Swaan PW. PubMed

Drug distribution

  • J Pharmacol Exp Ther. 2018;366:37-45. Hepatobiliary disposition of Atovaquone: a case of mechanistically unusual biliary clearance. Patel M, Johnson M, Sychterz CJ, Lewis GJ, Watson C, Ellens H, Polli JW, Zamek-Gliszczynski MJ. PubMed
  • Drug Metab Pharmacokinet. 2018;33:164-172.Total hepatocellular disposition profiling of rosuvastatin and pitavastatin in sandwich-cultured human hepatocytes. Kanda K, Takahashi R, Yoshikado T, Sugiyama Y. PubMed

Drug-drug inhibition

  • Mol Pharm. 2018;15:3060-3068. In silico and in vitro assessment of OATP1B1 inhibition in drug discovery. Danielson ML, Sawada GA, Raub TJ, Desai PV. PubMed
  • Drug Metab Dispos. 2018;46:1179-1189. Simultaneous assessment of transporter-mediated drug-drug interactions using a probe drug cocktail in Cynomolgus monkey. Kosa RE, Lazzaro S, Bi YA, Tierney B, Gates D, Modi S, Costales C, Rodrigues AD, Tremaine LM, Varma MV. 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
  • J Pharm Pharm Sci. 2018;21:236-246. Therapeutic doses of Eltrombopag do not inhibit hepatic BCRP in healthy volunteers: intravenous Ceftriaxone as a model. Neves DV, Vieira CP, Rocha A, Lanchote VL. PubMed
  • Drug Metab Dispos. 2018;46:1212–1225. The drug-drug interaction potential of antiviral agents for the treatment of chronic hepatitis C infection. Garrison KL, German P, Mogalian E, Mathias A. PubMed

Drug-induced cholestasis

  • Expert Opin Drug Metab Toxicol. 2018;14:721-738. Predicting drug-induced cholestasis: preclinical models. Petrov PD, Fernández-Murga ML, López-Riera M, Goméz-Lechón MJ, Castell JV, Jover R. PubMed

Hepatocyte uptake of drugs

  • Drug Metab Dispos. 2018;46:989-1000. Predicting human clearance of Organic Anion Transporting Polypeptide substrates using Cynomolgus monkey: in vitro-in vivo scaling of hepatic uptake clearance. De Bruyn T, Ufuk A, Cantrill C, Kosa RE, Bi YA, Niosi M, Modi S, Rodrigues AD, Tremaine LM, Varma MVS, Galetin A, Houston JB. PubMed
  • Mol Pharm. 2018;15:2277-2288. Relative activity factor (RAF)-based scaling of uptake clearance mediated by Organic Anion Transporting Polypeptide (OATP)1B1 and OATP1B3 in human hepatocytes. Izumi S, Nozaki Y, Kusuhara H, Hotta K, Mochizuki T, Komori T, Maeda K, Sugiyama Y. PubMed
  • Drug Metab Dispos. 2018;46:953-963. Prediction and quantification of hepatic transporter-mediated uptake of Pitavastatin utilizing a combination of the relative activity factor approach and mechanistic modeling. Mitra P, Weinheimer S, Michalewicz M, Taub ME. PubMed
  • J Pharm Sci. 2018;107:1791-1797. Extrapolation of the hepatic clearance of drugs in the absence of albumin in vitro to that in the presence of albumin in vivo: comparative assessment of 2 extrapolation models based on the albumin-mediated hepatic uptake theory and limitations and mechanistic insights. Poulin P, Haddad S. PubMed

NTCP inhibition

  • Hepatology. 2018;in press.  Na+-taurocholate cotransporting polypeptide inhibition has hepatoprotective effects in cholestasis in mice. Slijepcevic D, Roscam Abbing RLP, Fuchs CD, Haazen LCM, Beuers U, Trauner M, Oude Elferink RPJ, van de Graaf SFJ. PubMed