Transporter regulation

  • Drug Metab Dispos. 2018;46:259-267. The phenomenon of albumin-mediated hepatic uptake of Organic Anion Transport Polypeptide substrates: prediction of the in vivo Uptake clearance from the in vitro uptake by isolated hepatocytes using a facilitated-dissociation model. Miyauchi S, Masuda M, Kim SJ, Tanaka Y, Lee KR, Iwakado S, Nemoto M, Sasaki S, Shimono K, Tanaka Y, Sugiyama Y. The authors suggest that the facilitated-dissociation model (in which the interaction of ligand-albumin complex with cell surface enhances the dissociation of that complex to provide unbound ligand for uptake to hepatocytes) is applicable to albumin-mediated hepatic uptake via organic anion transporters and hepatic uptake clearance in vivo. PubMed
  • J Pharmacol Exp Ther. 2018;364:390-398. Organic Anion Transporter 2 mediates hepatic uptake of Tolbutamide, a CYP2C9 probe drug. Bi YA, Mathialagan S, Tylaska L, Fu M, Keefer J, Vildhede A, Costales C, Rodrigues AD, Varma MVS. The study evidences the role of OAT2-mediated hepatic uptake in the pharmacokinetics of tolbutamide. PubMed

Pharmacokinetic models

  • Clin Sci (Lond). 2018;2018;132:813-824. Imaging. Quantification of hepatic perfusion and hepatocyte function with dynamic gadoxetic acid-enhanced MR imaging in patients with chronic liver disease. Leporq B, Daire JL, Pastor CM, Deltenre P, Sempoux C, Schmidt S, Van Beers BE. This study quantifies hepatic perfusion and hepatocyte function with dynamic gadoxetic acid-enhanced MR imaging. Parameters of hepatocyte function are related to fibrosis extension. PubMed
  • CPT Pharmacometrics Syst Pharmacol. 2017;6:228-238. Investigating transporter-mediated drug-drug interactions using a physiologically based pharmacokinetic model of Rosuvastatin. Wang Q, Zheng M, Leil T. PubMed
  • Drug Metab Dispos. 2018;46:346-356. A study on pharmacokinetics of Bosentan with systems modeling, Part 1: translating systemic plasma concentration to liver exposure in healthy subjects. Li R, Niosi M, Johnson N, Tess DA, Kimoto E, Lin J, Yang X, Riccardi KA, Ryu S, El-Kattan AF, Maurer TS, Tremaine LM, Di L. PubMed
  • Drug Metab Dispos. 2018;46:357-366. A study on pharmacokinetics of Bosentan with systems modeling, Part 2: prospectively predicting systemic and liver exposure in healthy subjects. Li R, Kimoto E, Niosi M, Tess DA, Lin J, Tremaine LM, Di L. PubMed

Endogenous markers of transporter function

  • Clin Pharmacol Ther. 2018;103:434-448. Endogenous probes for drug transporters: balancing vision with reality. Rodrigues AD, Taskar KS, Kusuhara H, Sugiyama Y. PubMed

Hepatic drug clearance: revisiting principles

  • Clin Pharmacol Ther. 2018;103:521-525. The universally unrecognized assumption in predicting drug clearance and organ extraction ratio. Benet LZ, Liu S, Wolfe AR. PubMed
  • Clin Pharmacol Ther. 2018;103:386-388. Commentary on "The universally unrecognized assumption in predicting drug clearance and organ extraction ratio". Rowland M, Pang KS. PubMed
  • Clin Pharmacol Ther. 2018;103:388-389. Revisiting principles behind drug clearance and organ extraction. Rostami-Hodjegan A. PubMed

Transporter and toxicity

  • J Clin Invest. 2018;128:816-825. OATP1B2 deficiency protects against paclitaxel-induced neurotoxicity. Leblanc AF, Sprowl JA, Alberti P, Chiorazzi A, Arnold WD, Gibson AA, Hong KW, Pioso MS, Chen M, Huang KM, Chodisetty V, Costa O, Florea T, de Bruijn P, Mathijssen RH, Reinbolt RE, Lustberg MB, Sucheston-Campbell LE, Cavaletti G, Sparreboom A, Hu S. PubMed
  • Drug Metab Dispos. 2017;45:1240-1244. Colistin is substrate of the carnitine/organic cation transporter 2 (OCTN2, SLC22A5). Visentin M, Gai Z, Torozi A, Hiller C, Kullak-Ublick GA. PubMed

Drug-induced liver injury

  • Hepatology. 2018 Jan 22. Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort. Church RJ, Kullak-Ublick GA, Aubrecht J, Bonkovsky HL, Chalasani N, Fontana RJ, Goepfert JC, Hackman F, King NMP, Kirby S, Kirby P, Marcinak J, Ormarsdottir S, Schomaker SJ, Schuppe-Koistinen I, Wolenski F, Arber N, Merz M, Sauer JM, Andrade RJ, van Bömmel F, Poynard T, Watkins PB. PubMed
  • Toxicol Sci. 2018; in press. Bile acid sequestration by cholestyramine mitigates FGFR4 inhibition-induced ALT elevation. Schadt HS, Wolf A, Mahl JA, Wuersch K, Couttet P, Schwald M, Fischer A, Lienard , Emotte C, Teng CH, Skuba E, Richardson TA, Manenti L, Weiss A, Graus Porta D, Fairhurst RA, Kullak-Ublick GA, Chibout SD, Pognan F, Kluwe W, Kinyamu-Akunda J. PubMed

Potential benefits of bilirubin

  • Hepatology. 2018;67:1609-1619. Systemic regulation of bilirubin homeostasis: Potential benefits of hyperbilirubinemia. Fujiwara R, Haag M, Schaeffeler E, Nies AT, Zanger UM, Schwab M. The review highlights new understanding of bilirubin. PubMed
  • Trends Endocrinol Metab. 2018;29:140-150. Bilirubin in the Liver-Gut signaling axis. Hamoud AR, Weaver L, Stec DE, Hinds TD. PubMed

Liver physiology

  • Hepatology. 2018;67:1624-1627. Hydrodynamics of bile flow: Lessons from computational modeling. Jansen PLM. PubMed