Bile acid transport

  • Pharmacol Res Perspect. 2017;5. Obeticholic acid, a selective farnesoid X receptor agonist, regulates bile acid homeostasis in sandwich-cultured human hepatocytes. Zhang Y, Jackson JP, St Claire RL, Freeman K, Brouwer KR, Edwards JE. PubMed
  • Mol Pharmacol. 2017;92:401-413. Molecular mechanism of Taurocholate transport by the Bile Salt Export Pump, an ABC transporter associated with intrahepatic cholestasis. Sohail MI, Schmid D, Wlcek K, Spork M, Szakács G, Trauner M, Stockner T, Chiba P. PubMed
  • J Pharm Sci. 2017;106:2412-2419. Identification of bile acids responsible for inhibiting the Bile Salt Export Pump, leading to bile acid accumulation and cell toxicity in rat hepatocytes. Oizumi K, Sekine S, Fukagai M, Susukida T, Ito K. PubMed This study measured the accumulation of 12 bile acids in rat sandwich-cultured hepatocytes in the presence of 10 μM cyclosporine A (CsA), which inhibits BSEP, and 50 μM CsA, which further inhibits basolateral bile acid efflux transporters. The accumulation of all bile acids was observed with 10 μM CsA. Only chenodeoxycholic acid, deoxycholic acid (DCA), and glyco-DCA induced toxicity with 10 μM CsA. Taurolithocholic acid, glyco-CDCA, and glycocholic acid increased hepatocyte toxicity with 50 μM CsA without additional accumulation.
  • J Comput Aided Mol Des. 2017;31:507-521. Structure based classification for bile salt export pump (BSEP) inhibitors using comparative structural modeling of human BSEP. Jain S, Grandits M, Richter L, Ecker GF. PubMed

Transporter expression in liver diseases

  • J Pharm Sci. 2017;106:2282-2294. Effect of liver disease on hepatic transporter expression and function. Thakkar N, Slizgi JR, Brouwer KLR. PubMed Liver disease alter the disposition of xenobiotics and endogenous substances. Regulatory agencies recommend to study the effect of liver disease on drugs under development and recent alterations of the expression and function of hepatobiliary transport proteins in liver disease have been published. This review summarizes recent developments in the field, which may have implications for understanding altered disposition, safety, and efficacy of new and existing drugs. Expression and function of hepatic transporters in cholestasis, hepatitis C infection, hepatocellular carcinoma, human immunodeficiency virus infection, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, and primary biliary cirrhosis are reviewed. In the absence of clinical data, nonclinical information in animal models is presented.
  • J Chromatogr B Analyt Technol Biomed Life Sci. 2017;1061-1062:356-363.  Development of a rapid and sensitive multiple reaction monitoring proteomic approach for quantification of transporters in human liver tissue. Wang L, Rubadue KJ, Alberts J, Bedwell DW, Ruterbories KJ. PubMed


  • J Pharm Sci. 2017;106(9):2558-2565. Possible role of Organic Cation Transporters in the distribution of [11C]Sulpiride, a dopamine D2 receptor antagonist. Takano H, Ito S, Zhang X, Ito H, Zhang MR, Suzuki H, Maeda K, Kusuhara H, Suhara T, Sugiyama Y. PubMed The authors synthesized [11C]sulpiride (atypical antipsychotic drug) as a positron emission tomography probe for investigating the drug distribution in the human body. Whole-body positron emission tomography imaging demonstrates that [11C]sulpiride accumulate exceedingly in the bladder, followed by liver, gall bladder, and kidney 30 min after the injection. In vitro experiments evidence that sulpiride is a substrate of hOCT1, hOCT2, hMATE1, and hMATE2-K.

Transporter regulation

  • PLoS One. 2017;12:e0180257. Organic anion transporting polypeptide 1B3 can form homo- and hetero-oligomers. Zhang Y, Boxberger KH1, Hagenbuch B. PubMed Organic anion transporting polypeptide 1B3 can form homo- and hetero-oligomers with OATP1B1 and NTCP, suggesting a potential co-regulation of the involved transporters.
  • Eur J Pharm Sci. 2017;106:302-312. β2-adrenergic receptor-mediated in vitro regulation of human hepatic drug transporter expression by epinephrine. Mayati A, Moreau A, Denizot C2, Stieger B, Parmentier Y, Fardel O. PubMed The catecholamine epinephrine is known to repress expression of hepatic drug metabolizing enzymes such as cytochromes P-450. The present study determines whether epinephrine may also target expression of main hepatic drug transporters. Results indicate that epinephrine regulates in vitro expression of main hepatic drug transporters in a β2-ADR/adenylate cyclase/cAMP-dependent manner. Hepatic drug transport appears therefore as a target of the β2-adrenergic system, which may have to deserve attention for drugs interacting with β2-ADRs.

Transport of compounds: Cilostazol, Glyburide

  • J Pharm Sci. 2017;106:2515-2523. Organic Anion-Transporting Polypeptide and efflux transporter-mediated hepatic uptake and biliary excretion of Cilostazol and Its metabolites in rats and humans. Wang C, Huo X, Wang C, Meng Q, Liu Z, Sun P, Cang J, Sun H, Liu K. PubMed
  • Drug Metab Dispos. 2017;45:737-747. Transporter-mediated disposition, clinical pharmacokinetics and cholestatic potential of Glyburide and its primary active metabolites. Li R, Bi YA, Vildhede A, Scialis RJ, Mathialagan S, Yang X, Marroquin LD, Lin J, Varma MVS. PubMed

Experimental models in transporter research

  • J Pharm Sci. 2017;106:2302-2311. Recent progress in hepatocyte culture models and their application to the assessment of drug metabolism, transport, and toxicity in drug discovery: the value of tissue engineering for the successful development of a microphysiological system. Tetsuka K, Ohbuchi M, Tabata K. PubMed
  • Methods. 2017;128:40-51. Using quantitative intravital multiphoton microscopy to dissect hepatic transport in rats. Dunn KW, Ryan JC. PubMed
  • J Pharm Sci. 2017;106:2295-2301. Model systems for studying the role of canalicular efflux transporters in drug-induced cholestatic liver disease. Stieger B, Mahdi ZM2. PubMed

Drug-drug interactions

  • Xenobiotica. 2017;21:1-10. In vitro drug-drug interactions of budesonide: inhibition and induction of transporters and cytochrome P450 enzymes. Chen N, Cui D, Wang Q, Wen Z, Finkelman RD, Welty D. PubMed
  • J Pharm Sci. 2017;106:2123-2135. Pretreatment with rifampicin and Tyrosine Kinase Inhibitor Dasatinib potentiates the inhibitory effects toward OATP1B1- and OATP1B3-mediated transport. Pahwa S, Alam K, Crowe A, Farasyn T, Neuhoff S, Hatley O, Ding K, Yue W. PubMed