The Effect of Uremic Solutes on the Organic Cation Transporter 2

Journal of Pharmaceutical Sciences

Volumn 106, Issue 9, 2017, Pages 2551-2557

  Cheung, Kit Wun Kathy ^a,b   Hsueh, Chia Hsiang ^a,b   Zhao, Ping ^b   Meyer, Timothy W ^c   Zhang, Lei ^b   Huang, Shiew Mei ^b   Giacomini, Kathleen M ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

^c STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

disease states; OCT; organic cation transporters; regulatory science; renal clearance

Indexed keywords

3 CARBOXY 4 METHYL 5 PROPYL 2 FURAN PROPANOIC ACID; 6 N CARBOXYMETHYLLYSINE; CARBON 14; CREATINE; DEXPRAMIPEXOLE; DIMETHYLAMINE; DOPA; GLUCURONIDE; GLUTATHIONE DISULFIDE; HOMOCYSTEINE; INDOXYL BETA GLUCURONIDE; LAMIVUDINE; MALONALDEHYDE; METFORMIN; NEOPTERIN; ORGANIC CATION TRANSPORTER 2; OROTIC ACID; PENTOSIDINE; PHENYLACETIC ACID; PILSICAINIDE; PROPIONIC ACID DERIVATIVE; SEPANTRONIUM BROMIDE; TIOTROPIUM BROMIDE; TRIMETHYLAMINE; UNCLASSIFIED DRUG; UREMIC SOLUTE; UREMIC TOXIN; URIC ACID; GLUCURONIC ACID; INDOLE DERIVATIVE; INDOXYL GLUCURONIDE; METHYLAMINE; TOXIN; UREMIA MIDDLE MOLECULE TOXINS;

ARTICLE; CHRONIC KIDNEY FAILURE; CONTROLLED STUDY; DISEASE COURSE; DRUG CLEARANCE; DRUG ELIMINATION; DRUG PROTEIN BINDING; DRUG UPTAKE; GLOMERULUS FILTRATION RATE; HEK293 CELL LINE; HUMAN; HUMAN CELL; IC50; ISOTOPE LABELING; KIDNEY TUBULE EXCRETION; PROTEIN ANALYSIS; CHEMISTRY; DRUG EFFECT; KIDNEY; METABOLISM; TRANSPORT AT THE CELLULAR LEVEL; UREMIA;

BIOLOGICAL TRANSPORT; DIMETHYLAMINES; GLOMERULAR FILTRATION RATE; GLUCURONATES; GLUTATHIONE DISULFIDE; HEK293 CELLS; HOMOCYSTEINE; HUMANS; INDOLES; KIDNEY; MALONDIALDEHYDE; METFORMIN; METHYLAMINES; ORGANIC CATION TRANSPORTER 2; RENAL INSUFFICIENCY, CHRONIC; TOXINS, BIOLOGICAL; UREMIA;

EID: 85023197198     PISSN: 00223549     EISSN: 15206017     Source Type: Journal    
DOI: 10.1016/j.xphs.2017.04.076     Document Type: Article

References (52)

1. Giacomini, K.M., Huang, S.M., Tweedie, D.J., et al. Membrane transporters in drug development. Nat Rev Drug Discov 9:3 (2010), 215–236.
2. Huang, S.-M., Woodcock, J., Transporters in drug development: advancing on the Critical Path. Nat Rev Drug Discov 9:3 (2010), 175–176.
3. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research. Guidance for Industry. Drug Interaction Studies–Study Design, Data Analysis, and Implications for Dosing and Labeling. Draft Guidance. 2012, U.S. FDA Website, Silver Spring, MD Available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm292362.pdf Accessed August 17, 2016.
4. European Medicines Agency. Guideline on the Investigation of Drug Interactions. Committee for Human Medicinal Products. European Medicines Agency. 2012, EMA, London, UK Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/07/WC500129606.pdf Accessed August 17, 2016.
5. Pharmaceuticals Medical Devices Agency (PMDA). Draft Guideline on Drug Interactions (2013). 2013, PMDA, Tokyo, Japan Available at: http://search.e-gov.go.jp/servlet/Public?CLASSNAME=PCMMSTDETAIL&id=495130206 Accessed December 19, 2016.
6. Lepist, E.-I., Ray, A.S., Renal transporter-mediated drug-drug interactions: are they clinically relevant?. J Clin Pharmacol 56 Suppl 7 (2016), S73–S81.
7. Hsueh, C.-H., Yoshida, K., Zhao, P., et al. Identification and quantitative assessment of uremic solutes as inhibitors of renal organic anion transporters, OAT1 and OAT3. Mol Pharm 13:9 (2016), 3130–3140.
8. National Kidney Foundation. Fast Facts–The National Kidney Foundation. 2016, National Kidney Foundation, New York, NY Available at: https://www.kidney.org/news/newsroom/factsheets/FastFacts#Ref Accessed December 28, 2016.
9. Duranton, F., Cohen, G., De Smet, R., et al. Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol 23:7 (2012), 1258–1270.
10. Vanholder, R., Glorieux, G., De Smet, R., Lameire, N., European Uremic Toxin Work Group. New insights in uremic toxins. Kidney Int Suppl 84 (2003), S6–S10.
11. Kimura, N., Masuda, S., Tanihara, Y., et al. Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet 20:5 (2005), 379–386.
12. Chen, Y., Li, S., Brown, C., et al. Effect of genetic variation in the organic cation transporter 2 on the renal elimination of metformin. Pharmacogenet Genomics 19:7 (2009), 497–504.
13. Türck, D., Weber, W., Sigmund, R., et al. Pharmacokinetics of intravenous, single-dose tiotropium in subjects with different degrees of renal impairment. J Clin Pharmacol 44:2 (2004), 163–172.
14. Sambol, N.C., Chiang, J., Lin, E.T., et al. Kidney function and age are both predictors of pharmacokinetics of metformin. J Clin Pharmacol 35:11 (1995), 1094–1102.
15. Takabatake, T., Ohta, H., Yamamoto, Y., et al. Pharmacokinetics of SUN 1165, a new antiarrhythmic agent, in renal dysfunction. Eur J Clin Pharmacol 40:4 (1991), 411–414.
16. Aoyama, Y., Nishimura, T., Sawamoto, T., Satoh, T., Katashima, M., Nakagawa, K., Pharmacokinetics of sepantronium bromide (YM155), a small-molecule suppressor of survivin, in Japanese patients with advanced solid tumors: dose proportionality and influence of renal impairment. Cancer Chemother Pharmacol 70:3 (2012), 373–380.
17. Johnson, M.A., Verpooten, G.A., Daniel, M.J., et al. Single dose pharmacokinetics of lamivudine in subjects with impaired renal function and the effect of haemodialysis. Br J Clin Pharmacol 46:1 (1998), 21–27.
18. Heald, A.E., Hsyu, P.H., Yuen, G.J., Robinson, P., Mydlow, P., Bartlett, J.A., Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction. Antimicrob Agents Chemother 40:6 (1996), 1514–1519.
19. U.S. Food and Drug Administration. Spiriva (NDA 021395)–Part 1. Clinical Pharmacology and Biopharmaceutics Review(s) 2001. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-395.pdf_Spiriva_BioPharmr_P1.pdf Accessed May 29, 2016.
20. U.S. Food and Drug Administration. Spiriva (NDA 021395)–Part 2. Clinical Pharmacology and Biopharmaceutics Review(s) 2001. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-395.pdf_Spiriva_BioPharmr_P2.pdf Accessed May 30, 2016.
21. U.S. Food and Drug Administration. Glucophage (NDA 020357). Clinical Pharmacology and Biopharmaceutics Review(s) 2000. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20357S019_Glucophage_biopharmr.pdf Accessed May 12, 2016.
22. U.S. Food and Drug Administration. Glucophage XR (NDA 021202). Clinical Pharmacology and Biopharmaceutics Review(s) 1999. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-202_Glucophage_biopharmre.pdf Accessed May 30, 2016.
23. U.S. Food and Drug Administration. Glumetza (NDA 021748). Clinical Pharmacology and Biopharmaceutics Review(s) 2005. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021748s000_Glumetza_ClinPharmR.pdf Accessed May 30, 2016.
24. U.S. Food and Drug Administration. Epivir (NDA 020564). Clinical Pharmacology and Biopharmaceutics Review(s) 1999. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/020564_S020_Epivir.pdf Accessed May 30, 2016.
25. He, P., Kerr, D., Marbury, T., et al. Pharmacokinetics of renally excreted drug dexpramipexole in subjects with impaired renal function. J Clin Pharmacol 54:12 (2014), 1383–1390.
26. Centers for Disease Control and Prevention. High Blood Pressure (Hypertension) Information | cdc.gov. 2016, Centers for Disease Control and Prevention, Atlanta, GA Available at: https://www.cdc.gov/bloodpressure/ Accessed December 28, 2016.
27. Coresh, J., Selvin, E., Stevens, L.A., et al. Prevalence of chronic kidney disease in the United States. JAMA 298:17 (2007), 2038–2047.
28. Lisowska-Myjak, B., Uremic toxins and their effects on multiple organ systems. Nephron Clin Pract 128:3-4 (2014), 303–311.
29. Ciarimboli, G., Lancaster, C.S., Schlatter, E., et al. Proximal tubular secretion of creatinine by organic cation transporter OCT2 in cancer patients. Clin Cancer Res 18:4 (2012), 1101–1108.
30. Schophuizen, C.M.S., Wilmer, M.J., Jansen, J., et al. Cationic uremic toxins affect human renal proximal tubule cell functioning through interaction with the organic cation transporter. Pflugers Arch 465:12 (2013), 1701–1714.
31. Kimura, N., Masuda, S., Katsura, T., Inui, K., Transport of guanidine compounds by human organic cation transporters, hOCT1 and hOCT2. Biochem Pharmacol 77:8 (2009), 1429–1436.
32. Kido, Y., Matsson, P., Giacomini, K.M., Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. J Med Chem 54:13 (2011), 4548–4558.
33. Hacker, K., Maas, R., Kornhuber, J., Fromm, M.F., Zolk, O., Substrate-dependent inhibition of the human organic cation transporter OCT2: a comparison of metformin with experimental substrates. PLoS ONE, 10(9), 2015, e0136451.
34. Bricker, N.S., Morrin, P.A., Kime, S.W., The pathologic physiology of chronic Bright's disease. An exposition of the “intact nephron hypothesis”. Am J Med 28 (1960), 77–98.
35. Bohle, A., Christ, H., Grund, K.E., Mackensen, S., The role of the interstitium of the renal cortex in renal disease. Contrib Nephrol 16 (1979), 109–114.
36. Ji, L., Masuda, S., Saito, H., Inui, K., Down-regulation of rat organic cation transporter rOCT2 by 5/6 nephrectomy. Kidney Int 62:2 (2002), 514–524.
37. Pedersen, L., Jensen, J.B., Wogensen, L., et al. Renal PET-imaging with (11)C-metformin in a transgenic mouse model for chronic kidney disease. EJNMMI Res, 6(1), 2016, 54.
38. Gong, L., Goswami, S., Giacomini, K.M., Altman, R.B., Klein, T.E., Metformin pathways: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics 22:11 (2012), 820–827.
39. Müller, F., König, J., Hoier, E., Mandery, K., Fromm, M.F., 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 86:6 (2013), 808–815.
40. Nakamura, T., Nakanishi, T., Haruta, T., Shirasaka, Y., Keogh, J.P., Tamai, I., Transport of ipratropium, an anti-chronic obstructive pulmonary disease drug, is mediated by organic cation/carnitine transporters in human bronchial epithelial cells: implications for carrier-mediated pulmonary absorption. Mol Pharm 7:1 (2010), 187–195.
41. Ito, S., Kusuhara, H., Yokochi, M., et al. Competitive inhibition of the luminal efflux by multidrug and toxin extrusions, but not basolateral uptake by organic cation transporter 2, is the likely mechanism underlying the pharmacokinetic drug-drug interactions caused by cimetidine in the kidney. J Pharmacol Exp Ther 340:2 (2012), 393–403.
42. Klatt, S., Fromm, M.F., König, J., Transporter-mediated drug-drug interactions with oral antidiabetic drugs. Pharmaceutics 3:4 (2011), 680–705.
43. Tahara, H., Kusuhara, H., Maeda, K., Koepsell, H., Fuse, E., Sugiyama, Y., Inhibition of oat3-mediated renal uptake as a mechanism for drug-drug interaction between fexofenadine and probenecid. Drug Metab Dispos 34:5 (2006), 743–747.
44. Lin, C.-J., Chen, H.-H., Pan, C.-F., et al. p-Cresylsulfate and indoxyl sulfate level at different stages of chronic kidney disease. J Clin Lab Anal 25:3 (2011), 191–197.
45. Lowenstein, J., Competition for organic anion transporters in chronic renal disease. Kidney Int, 82(9), 2012, 1033.
46. Keller, F., Maiga, M., Neumayer, H.-H., Lode, H., Distler, A., Pharmacokinetic effects of altered plasma protein binding of drugs in renal disease. Eur J Drug Metab Pharmacokinet 9:3 (1984), 275–282.
47. Vanholder, R., Van Landschoot, N., De Smet, R., Schoots, A., Ringoir, S., Drug protein binding in chronic renal failure: evaluation of nine drugs. Kidney Int 33:5 (1988), 996–1004.
48. Graingerrousseau, T., Mcelnay, J., Collier, P., The influence of disease on plasma protein binding of drugs. Int J Pharm 54:1 (1989), 1–13.
49. Klammt, S., Wojak, H.-J., Mitzner, A., et al. Albumin-binding capacity (ABiC) is reduced in patients with chronic kidney disease along with an accumulation of protein-bound uraemic toxins. Nephrol Dial Transpl 27:6 (2012), 2377–2383.
50. Levey, A.S., Coresh, J., Greene, T., et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 145:4 (2006), 247–254.
51. Levey, A.S., A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med, 130(6), 1999, 461.
52. Cockcroft, D.W., Gault, M.H., Prediction of creatinine clearance from serum creatinine. Nephron 16:1 (1976), 31–41.