Emtricitabine is a substrate of MATE1 but not of OCT1, OCT2, P-gp, BCRP or MRP2 transporters

References

• AIDSinfo. (2015). Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available from: http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf [last accessed 16 Nov 2015]
   Google Scholar
• Bang LM, Scott LJ. (2003). Emtricitabine: an antiretroviral agent for HIV infection. Drugs 63:2413. discussion 25–6
   PubMed Web of Science ®Google Scholar
• Bart J, Hollema H, Groen HJ, et al. (2004). The distribution of drug-efflux pumps, P-gp, BCRP, MRP1 and MRP2, in the normal blood-testis barrier and in primary testicular tumours. Eur J Cancer 40:2064–70
   PubMed Web of Science ®Google Scholar
• Bierman WF, Scheffer GL, Schoonderwoerd A, et al. (2010). Protease inhibitors atazanavir, lopinavir and ritonavir are potent blockers, but poor substrates, of ABC transporters in a broad panel of ABC transporter-overexpressing cell lines. J Antimicrob Chemother 65:1672–80
   PubMed Web of Science ®Google Scholar
• Bousquet L, Pruvost A, Didier N, et al. (2008). Emtricitabine: inhibitor and substrate of multidrug resistance associated protein. Eur J Pharm Sci 35:247–56
   PubMed Web of Science ®Google Scholar
• Brown KC, Paul S, Kashuba AD. (2009). Drug interactions with new and investigational antiretrovirals. Clin Pharmacokinet 48:211–41
   PubMed Web of Science ®Google Scholar
• Chan LM, Lowes S, Hirst BH. (2004). The ABCs of drug transport in intestine and liver: efflux proteins limiting drug absorption and bioavailability. Eur J Pharm Sci 21:25–51
   PubMed Web of Science ®Google Scholar
• Dickinson L, Khoo S, Back D. (2010). Pharmacokinetics and drug-drug interactions of antiretrovirals: an update. Antiviral Res 85:176–89
   PubMed Web of Science ®Google Scholar
• Emtriva® package insert. (2012). Emtriva package insert. Foster City (CA): Gilead Sciences
   Google Scholar
• FDA. (2012). Guidance for industry, drug interaction studies — study design, data analysis, implications for dosing, and labeling recommendations. Clinical Pharmacology. Silver Spring (MD): FDA
   Google Scholar
• Ford J, Khoo SH, Back DJ. (2004). The intracellular pharmacology of antiretroviral protease inhibitors. J Antimicrob Chemother 54:982–90
   PubMed Web of Science ®Google Scholar
• Giacomini KM, Huang SM, Tweedie DJ, et al. (2010). Membrane transporters in drug development. Nat Rev Drug Discov 9:215–36
   PubMed Web of Science ®Google Scholar
• Gorboulev V, Ulzheimer JC, Akhoundova A, et al. (1997). Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol 16:871–81
   PubMed Web of Science ®Google Scholar
• Holmstock N, Annaert P, Augustijns P. (2012). Boosting of HIV protease inhibitors by ritonavir in the intestine: the relative role of cytochrome P450 and P-glycoprotein inhibition based on Caco-2 monolayers versus in situ intestinal perfusion in mice. Drug Metab Dispos 40:1473–7
   PubMed Web of Science ®Google Scholar
• Huang F, Scholl P, Huang DB, et al. (2011). Concomitant administration of BILR 355/r with emtricitabine/tenofovir disoproxil fumarate increases exposure to emtricitabine and tenofovir: a randomized, open-label, prospective study. Basic Clin Pharmacol Toxicol 108:163–70
   PubMed Web of Science ®Google Scholar
• Huang SM, Strong JM, Zhang L, et al. (2008). New era in drug interaction evaluation: US Food and Drug Administration update on CYP enzymes, transporters, and the guidance process. J Clin Pharmacol 48:662–70
   PubMed Web of Science ®Google Scholar
• Jung N, Lehmann C, Rubbert A, et al. (2008). Relevance of the organic cation transporters 1 and 2 for antiretroviral drug therapy in human immunodeficiency virus infection. Drug Metab Dispos 36:1616–23
   PubMed Web of Science ®Google Scholar
• Kempf DJ, Marsh KC, Kumar G, et al. (1997). Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir. Antimicrob Agents Chemother 41:654–60
   PubMed Web of Science ®Google Scholar
• Kido Y, Matsson P, Giacomini KM. (2011). Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. J Med Chem 54:4548–58
   PubMed Web of Science ®Google Scholar
• Kis O, Robillard K, Chan GN, Bendayan R. (2010). The complexities of antiretroviral drug-drug interactions: role of ABC and SLC transporters. Trends Pharmacol Sci 31:22–35
   PubMed Web of Science ®Google Scholar
• Koepsell H, Lips K, Volk C. (2007). Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications. Pharm Res 24:1227–51
   PubMed Web of Science ®Google Scholar
• König J, Müller F, Fromm MF. (2013). Transporters and drug-drug interactions: important determinants of drug disposition and effects. Pharmacol Rev 65:944–66
   PubMed Web of Science ®Google Scholar
• König J, Zolk O, Singer K, et al. (2011). Double-transfected MDCK cells expressing human OCT1/MATE1 or OCT2/MATE1: determinants of uptake and transcellular translocation of organic cations. Br J Pharmacol 163:546–55
   PubMed Web of Science ®Google Scholar
• Lee G, Dallas S, Hong M, Bendayan R. (2001). Drug transporters in the central nervous system: brain barriers and brain parenchyma considerations. Pharmacol Rev 53:569–96
   PubMed Web of Science ®Google Scholar
• Lepist EI, Ray AS. (2012). Renal drug-drug interactions: what we have learned and where we are going. Expert Opin Drug Metab Toxicol 8:433–48
   PubMed Web of Science ®Google Scholar
• Minuesa G, Volk C, Molina-Arcas M, et al. (2009). Transport of lamivudine [(-)-beta-L-2′,3′-dideoxy-3′-thiacytidine] and high-affinity interaction of nucleoside reverse transcriptase inhibitors with human organic cation transporters 1, 2, and 3. J Pharmacol Exp Ther 329:252–61
   PubMed Web of Science ®Google Scholar
• Morrissey KM, Stocker SL, Wittwer MB, et al. (2013). Renal transporters in drug development. Annu Rev Pharmacol Toxicol 53:503–29
   PubMed Web of Science ®Google Scholar
• Motohashi H, Inui K. (2013). Organic cation transporter OCTs (SLC22) and MATEs (SLC47) in the human kidney. AAPS J 15:581–8
   PubMed Web of Science ®Google Scholar
• Motohashi H, Sakurai Y, Saito H, et al. (2002). Gene expression levels and immunolocalization of organic ion transporters in the human kidney. J Am Soc Nephrol 13:866–74
   PubMed Web of Science ®Google Scholar
• Moyle G. (2001). Use of HIV protease inhibitors as pharmacoenhancers. AIDS Read 11:87–98. quiz 107–8
   PubMedGoogle Scholar
• Müller F, Fromm MF. (2011). Transporter-mediated drug-drug interactions. Pharmacogenomics 12:1017–37
   PubMed Web of Science ®Google Scholar
• Müller F, König J, Glaeser H, et al. (2011). Molecular mechanism of renal tubular secretion of the antimalarial drug chloroquine. Antimicrob Agents Chemother 55:3091–8
   PubMed Web of Science ®Google Scholar
• Müller F, König J, Hoier E, et al. (2013). Role of organic cation transporter OCT2 and multidrug and toxin extrusion proteins MATE1 and MATE2-K for transport and drug interactions of the antiviral lamivudine. Biochem Pharmacol 86:808–15
   PubMed Web of Science ®Google Scholar
• Nakatani-Freshwater T, Taft DR. (2008a). Renal excretion of emtricitabine I: effects of organic anion, organic cation, and nucleoside transport inhibitors on emtricitabine excretion. J Pharm Sci 97:5401–10
   PubMed Web of Science ®Google Scholar
• Nakatani-Freshwater T, Taft DR. (2008b). Renal excretion of emtricitabine II. effect of trimethoprim on emtricitabine excretion: in vitro and in vivo studies. J Pharm Sci 97:5411–20
   PubMed Web of Science ®Google Scholar
• Neumanova Z, Cerveny L, Ceckova M, Staud F. (2014). Interactions of tenofovir and tenofovir disoproxil fumarate with drug efflux transporters ABCB1, ABCG2, and ABCC2; role in transport across the placenta. AIDS 28:9–17
   PubMed Web of Science ®Google Scholar
• Neumanova Z, Cerveny L, Ceckova M, Staud F. (2015a). Role of ABCB1, ABCG2, ABCC2 and ABCC5 transporters in placental passage of zidovudine. Biopharm Drug Dispos 37:28–38
   Web of Science ®Google Scholar
• Neumanova Z, Cerveny L, Greenwood SL, et al. (2015b). Effect of drug efflux transporters on placental transport of antiretroviral agent abacavir. Reprod Toxicol 57:176–82
   PubMed Web of Science ®Google Scholar
• Nies AT, Damme K, Schaeffeler E, Schwab M. (2012). Multidrug and toxin extrusion proteins as transporters of antimicrobial drugs. Expert Opin Drug Metab Toxicol 8:1565–77
   PubMed Web of Science ®Google Scholar
• Otsuka M, Matsumoto T, Morimoto R, et al. (2005). A human transporter protein that mediates the final excretion step for toxic organic cations. Proc Natl Acad Sci USA 102:17923–8
   PubMed Web of Science ®Google Scholar
• Staud F, Cerveny L, Ahmadimoghaddam D, Ceckova M. (2013). Multidrug and toxin extrusion proteins (MATE/SLC47); role in pharmacokinetics. Int J Biochem Cell Biol 45:2007–11
   PubMed Web of Science ®Google Scholar
• Staud F, Cerveny L, Ceckova M. (2012). Pharmacotherapy in pregnancy; effect of ABC and SLC transporters on drug transport across the placenta and fetal drug exposure. J Drug Target 20:736–63
   PubMed Web of Science ®Google Scholar
• Storch CH, Theile D, Lindenmaier H, et al. (2007). Comparison of the inhibitory activity of anti-HIV drugs on P-glycoprotein. Biochem Pharmacol 73:1573–81
   PubMed Web of Science ®Google Scholar
• Tsuda M, Terada T, Ueba M, et al. (2009). Involvement of human multidrug and toxin extrusion 1 in the drug interaction between cimetidine and metformin in renal epithelial cells. J Pharmacol Exp Ther 329:185–91
   PubMed Web of Science ®Google Scholar
• Weiss J, Rose J, Storch CH, et al. (2007a). Modulation of human BCRP (ABCG2) activity by anti-HIV drugs. J Antimicrob Chemother 59:238–45
   PubMed Web of Science ®Google Scholar
• Weiss J, Theile D, Ketabi-Kiyanvash N, et al. (2007b). Inhibition of MRP1/ABCC1, MRP2/ABCC2, and MRP3/ABCC3 by nucleoside, nucleotide, and non-nucleoside reverse transcriptase inhibitors. Drug Metab Dispos 35:340–4
   PubMed Web of Science ®Google Scholar
• WHO. (2013). Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. Geneva, Switzerland: WHO
   Google Scholar
• Wittwer MB, Zur AA, Khuri N, et al. (2013). Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem 56:781–95
   PubMed Web of Science ®Google Scholar
• Zamek-Gliszczynski MJ, Hoffmaster KA, Tweedie DJ, et al. (2012). Highlights from the International Transporter Consortium Second Workshop. Clin Pharmacol Ther 92:553–6
   PubMed Web of Science ®Google Scholar
• Zhang L, Zhang YD, Zhao P, Huang SM. (2009). Predicting drug-drug interactions: an FDA perspective. AAPS J 11:300–6
   PubMed Web of Science ®Google Scholar