Regulatory Science Perspectives on Transporter Studies in Drug Development

Drug Transporters: Molecular Characterization and Role in Drug Disposition: Second Edition

Volumn 9781118489932, Issue , 2014, Pages 473-490

  Lee, Sue Chih ^a   Zhang, Lei ^a   Huang, Shiew Mei ^a  

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

Author keywords

Drug development; Drug transporters; European Medicines Agency (EMA); Food and Drug Administration (FDA); Pharmaceutical and Medical Devices Agency (PMDA); Regulatory science perspectives

Indexed keywords

DRUG DEVELOPMENT; DRUG TRANSPORTER; EUROPEAN MEDICINE AGENCY; EUROPEAN MEDICINES AGENCIES; FOOD AND DRUG ADMINISTRATION; MEDICAL DEVICES; PHARMACEUTICAL AND MEDICAL DEVICE AGENCY; PHARMACEUTICAL DEVICES; REGULATORY SCIENCE PERSPECTIVE;

DRUG INTERACTIONS;

EID: 84927154577     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9781118705308.ch23     Document Type: Chapter

References (90)

1. Giacomini KM, Huang SM, Tweedie DJ, Benet LZ, Brouwer KL, Chu X, Dahlin A, Evers R, Fischer V, Hillgren KM, Hoffmaster KA, Ishikawa T, Keppler D, Kim RB, Lee CA, Niemi M, Polli JW, Sugiyama Y, Swaan PW, Ware JA, Wright SH, Yee SW, Zamek-Gliszczynski MJ, Zhang L. Membrane transporters in drug development. Nat Rev Drug Discov 2010;9 (3):215-236.
2. Giacomini KM, Sugiyama Y. Membrane transporters and drug response. In: Brunton LL, Chabner BA, Knollman BC, editors. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw Hill Medical; 2010.
3. Yokoo S, Yonezawa A, Masuda S, Fukatsu A, Katsura T, Inui K. Differential contribution of organic cation transporters, OCT2 and MATE1, in platinum agent-induced nephrotoxicity. Biochem Pharmacol 2007;74 (3):477-487.
4. Kim Y, Babu AR. Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes. Diabetes Metab Syndr Obes 2012;5:313-327.
5. INVOKANA Package Insert. 2013. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204042s000lbl.pdf. Accessed July 4, 2013.
6. Cundy KC. Clinical pharmacokinetics of the antiviral nucleotide analogues cidofovir and adefovir. Clin Pharmacokinet 1999;36 (2):127-143.
7. Guidance for Industry: Drug Interaction Studies-Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations (Draft). 2012. Available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM292362.pdf. Accessed July 4, 2013.
8. European Medicines Agency Guideline on the Investigation of Drug Interactions. 2012. Available at http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/07/WC500129606.pdf. Accessed July 4, 2013.
9. http://search.e-gov.go.jp/servlet/Public?CLASSNAME=PCMMSTDETAIL&id=495130206. Accessed April 10, 2014.
10. Presentations by Drs. Lei Zhang and Eva Gil Berglund in "Regulatory perspectives on transporter DDIs in drug development" at 2013 AAPS Workshop on Drug Transporters in ADME: From Bench to Bedside; 2013; Bethesda, MD. Available at http://www.aaps.org/Meetings_and_Professional_Development/Conference:Mini_Sites/AAPS_Workshop_on_Transporters_2013/Program/. Accessed March 6, 2014.
11. Tweedie D, Polli JW, Berglund EG, Huang SM, Zhang L, Poirier A, Chu X, Feng B. Transporter studies in drug development: experience to date and follow-up on decision trees from the international transporter consortium. Clin Pharmacol Ther 2013;94 (1):113-125.
12. FDA Pharmaceutical Science and Clinical Pharmacology Advisory Committee meeting; November 3-4, 2004. Available at http://www.fda.gov/ohrms/dockets/ac/cder04.html#Pharm-Science. Accessed July 4, 2013.
13. FDA Pharmaceutical Science and Clinical Pharmacology Advisory Committee meeting; October 18-19, 2006. Available at http://www.fda.gov/ohrms/dockets/ac/cder06.html#PharmScienc. Accessed July 4, 2013.
14. Hager WD, Fenster P, Mayersohn M, Perrier D, Graves P, Marcus FI, Goldman S. Digoxin-quinidine interaction pharmacokinetic evaluation. N Engl J Med 1979;300 (22):1238-1241.
15. Rameis H. Quinidine-digoxin interaction: are the pharmacokinetics of both drugs altered? Int J Clin Pharmacol Ther Toxicol 1985;23 (3):145-153.
16. Fromm MF, Kim RB, Stein CM, Wilkinson GR, Roden DM. Inhibition of P-glycoprotein-mediated drug transport: a unifying mechanism to explain the interaction between digoxin and quinidine [see comments]. Circulation 1999;99 (4):552-557.
17. Rengelshausen J, Goggelmann C, Burhenne J, Riedel KD, Ludwig J, Weiss J, Mikus G, Walter-Sack I, Haefeli WE. Contribution of increased oral bioavailability and reduced nonglomerular renal clearance of digoxin to the digoxin-clarithromycin interaction. Br J Cin Pharmacol 2003;56 (1):32-38.
18. Huang SM, Zhang L, Giacomini KM. The International Transporter Consortium: a collaborative group of scientists from academia, industry, and the FDA. Clin Pharmacol Ther 2010;87 (1):32-36.
19. FDA Pharmaceutical Science and Clinical Pharmacology Advisory Committee meeting; March 17, 2010. Available at http://www.fda.gov/AdvisoryCommittees/Calendar/ucm201691.htm. Accessed July 4, 2013.
20. Zamek-Gliszczynski MJ, Hoffmaster KA, Tweedie DJ, Giacomini KM, Hillgren KM. Highlights from the International Transporter Consortium second workshop. Clin Pharmacol Ther 2012;92 (5):553-556.
21. Hillgren KM, Keppler D, Zur AA, Giacomini KM, Stieger B, Cass CE, Zhang L. Emerging transporters of clinical importance: an update from the international transporter consortium. Clin Pharmacol Ther 2013;94 (1):52-63.
22. Zamek-Gliszczynski MJ, Lee CA, Poirier A, Bentz J, Chu X, Ellens H, Ishikawa T, Jamei M, Kalvass JC, Nagar S, Pang KS, Korzekwa K, Swaan PW, Taub ME, Zhao P, Galetin A. ITC recommendations for transporter kinetic parameter estimation and translational modeling of transport-mediated PK and DDIs in humans. Clin Pharmacol Ther 2013;94 (1):64-79.
23. Kalvass JC, Polli JW, Bourdet DL, Feng B, Huang SM, Liu X, Smith QR, Zhang LK, Zamek-Gliszczynski MJ. Why clinical modulation of efflux transport at the human blood-brain barrier is unlikely: the ITC evidence-based position. Clin Pharmacol Ther 2013;94 (1):80-94.
24. Brouwer KL, Keppler D, Hoffmaster KA, Bow DA, Cheng Y, Lai Y, Palm JE, Stieger B, Evers R. In vitro methods to support transporter evaluation in drug discovery and development. Clin Pharmacol Ther 2013;94 (1):95-112.
25. Chu X, Korzekwa K, Elsby R, Fenner K, Galetin A, Lai Y, Matsson P, Moss A, Nagar S, Rosania GR, Bai JP, Polli JW, Sugiyama Y, Brouwer KL. Intracellular drug concentrations and transporters: measurement, modeling, and implications for the liver. Clin Pharmacol Ther 2013;94 (1):126-141.
26. Giacomini KM, Balimane PV, Cho SK, Eadon M, Edeki T, Hillgren KM, Huang SM, Sugiyama Y, Weitz D, Wen Y, Xia CQ, Yee SW, Zimdahl H, Niemi M. International Transporter Consortium commentary on clinically important transporter polymorphisms. Clin Pharmacol Ther 2013;94 (1):23-26.
27. Giacomini KM, Huang SM. Transporters in drug development and clinical pharmacology. Clin Pharmacol Ther 2013;94 (1):3-9.
28. TYKERB Package Insert. 2013. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022059s016s017lbl.pdf. Accessed November 25, 2013.
29. Dorian P. Clinical pharmacology of dronedarone: implications for the therapy of atrial fibrillation. J Cardiovasc Pharmacol Ther 2010;15 (4 Suppl):15S-18S.
30. Jerling M. Clinical pharmacokinetics of ranolazine. Clin Pharmacokinet 2006;45 (5):469-491.
31. Mukwaya G, MacGregor T, Hoelscher D, Heming T, Legg D, Kavanaugh K, Johnson P, Sabo JP, McCallister S. Interaction of ritonavir-boosted tipranavir with loperamide does not result in loperamide-associated neurologic side effects in healthy volunteers. Antimicrob Agents Chemother 2005;49 (12):4903-4910.
32. APTIVUS Package Insert. 2012. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021814s013,022292s006lbl.pdf. Accessed July 4, 2013.
33. Kusuhara H, Furuie H, Inano A, Sunagawa A, Yamada S, Wu C, Fukizawa S, Morimoto N, Ieiri I, Morishita M, Sumita K, Mayahara H, Fujita T, Maeda K, Sugiyama Y. Pharmacokinetic interaction study of sulphasalazine in healthy subjects and the impact of curcumin as an in vivo inhibitor of BCRP. Br J Pharmacol 2012;166 (6):1793-1803.
34. CRESTOR Package Insert. 2012. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021366s026lbl.pdf. Accessed July 4, 2013.
35. Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther 2006;80 (6):565-581.
36. Kiser JJ, Gerber JG, Predhomme JA, Wolfe P, Flynn DM, Hoody DW. Drug/drug interaction between lopinavir/ritonavir and rosuvastatin in healthy volunteers. J Acquir Immune Defic Syndr 2008;47 (5):570-578.
37. Hirano M, Maeda K, Shitara Y, Sugiyama Y. Contribution of OATP2 (OATP1B1) and OATP8 (OATP1B3) to the hepatic uptake of pitavastatin in humans. J Pharmacol Exp Ther 2004;311 (1):139-146.
38. LIVALO Package Insert. 2012. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022363s010lbl.pdf. Accessed July 4, 2013.
39. PRAVACHOL Package Insert. 2012. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019898s063s064lbl.pdf. Accessed July 4, 2013.
40. Annaert P, Ye ZW, Stieger B, Augustijns P. Interaction of HIV protease inhibitors with OATP1B1, 1B3, and 2B1. Xenobiotica 2010;40 (3):163-176.
41. Somogyi A, Stockley C, Keal J, Rolan P, Bochner F. Reduction of metformin renal tubular secretion by cimetidine in man. Br J Clin Pharmacol 1987;23 (5):545-551.
42. MULTAQ Package Insert. 2013. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022425s021lbl.pdf. Accessed July 4, 2013.
43. Somogyi A, McLean A, Heinzow B. Cimetidine-procainamide pharmacokinetic interaction in man: evidence of competition for tubular secretion of basic drugs. Eur J Clin Pharmacol 1983;25 (3):339-345.
44. Kusuhara H, Ito S, Kumagai Y, Jiang M, Shiroshita T, Moriyama Y, Inoue K, Yuasa H, Sugiyama Y. Effects of a MATE protein inhibitor, pyrimethamine, on the renal elimination of metformin at oral microdose and at therapeutic dose in healthy subjects. Clin Pharmacol Ther 2011;89 (6):837-844.
45. Mischler TW, Sugerman AA, Willard DA, Brannick LJ, Neiss ES. Influence of probenecid and food on the bioavailability of cephradine in normal male subjects. J Clin Pharmacol 1974;14 (11-12):604-611.
46. Roberts DH, Kendall MJ, Jack DB, Welling PG. Pharmacokinetics of cephradine given intravenously with and without probenecid. Br J Clin Pharmacol 1981;11 (6):561-564.
47. Laskin OL, de Miranda P, King DH, Page DA, Longstreth JA, Rocco L, Lietman PS. Effects of probenecid on the pharmacokinetics and elimination of acyclovir in humans. Antimicrob Agents Chemother 1982;21 (5):804-807.
48. Vree TB, van den Biggelaar-Martea M, Verwey-van Wissen CP. Probenecid inhibits the renal clearance of frusemide and its acyl glucuronide. Br J Clin Pharmacol 1995;39 (6):692-695.
49. Iwaki K, Sakaeda T, Kakumoto M, Nakamura T, Komoto C, Okamura N, Nishiguchi K, Shiraki T, Horinouchi M, Okumura K. Haloperidol is an inhibitor but not substrate for MDR1/ P-glycoprotein. J Pharm Pharmacol 2006;58 (12):1617-1622.
50. JUXTAPID Package Insert. 2013. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203858s002lbl.pdf. Accessed July 4, 2013.
51. Ito K, Iwatsubo T, Kanamitsu S, Ueda K, Suzuki H, Sugiyama Y. Prediction of pharmacokinetic alterations caused by drugdrug interactions: metabolic interaction in the liver. Pharmacol Rev 1998;50 (3):387-412.
52. Zhang L, Zhang YD, Strong JM, Reynolds KS, Huang SM. A regulatory viewpoint on transporter-based drug interactions. Xenobiotica 2008;38 (7-8):709-724.
53. Agarwal S, Arya V, Zhang L. Review of P-gp Inhibition data in recently approved new drug applications: utility of the proposed [I1]/IC50 and [I2]/IC50 criteria in the P-gp decision tree. J Clin Pharmacol 2012;53 (2):228-233.
54. Ellens H, Deng S, Coleman J, Bentz J, Taub ME, Ragueneau-Majlessi I, Chung S, Heredi-Szabo K, Neuhof S, Palm JE, Balimane P, Zhang L, Jamei M, Hanna IH, O'Connor M, Bednarczyk D, Forsgard M, Chu X, Funk C, Guo A, Hillgren KM, Li L, Pak A, Perloff E, Rajaraman G, Salphati L, Taur J, Weitz D, Wortelboer H, Xia C, Xiao G, Yamagata T, Lee CA. Application of receiver operating characteristic (ROC) analysis to refine the prediction of potential digoxin drug interactions. Drug Metab Dispos 2013;41 (7):1367-1374.
55. Bentz JE, O'Connor M, Bednarczyk D, Coleman J, Lee CA, Palm JE, Pak A, Perloff ES, Reyner EL, Balimane P, Brannstrom M, Chu X, Funk C, Guo A, Hanna IH, Heredi-Szabo K, Hillgren KM, Li L, Hollnack-Pusch E, Jamei M, Lin X, Mason A, Neuhoff S, Patel A, Podila L, Plise E, Rajaraman G, Salphati L, Sands E, Taub ME, Taur J, Weitz D, Wortelboer H, Xia C, Xiao G, Yabut J, Yamagata T, Zhang LK, Ellens H. Variability in P-glycoprotein inhibitory potency (IC50) using various in vitro experimental systems: implications for universal digoxin DDI risk assessment decision criteria. Drug Metab Dispos 2013;41 (7):1347-1366.
56. Vaidyanathan J, Arya V, Agarwal S, Vieira MLT, Zhao P, Huang S-M, Zhang L. What criteria may be appropriate in determining the need for in vivo evaluation of a new molecular entity's (NME's) potential to inhibit OATP1B1 (organic anion transporting polypeptide 1B1). Clin Pharmacol Ther 2012;91:S53.
57. Zhang L, Huang SM. The role of transporters during drug development: Regulatory science perspectives from the FDA. In: Sugiyama Y, Steffansen B, editors. Transporters in Drug Development: Discovery, Optimization, Clinical Study and Regulation. New York: Springer; 2013.
58. Benet LZ. The drug transporter-metabolism alliance: uncovering and defining the interplay. Mol Pharm 2009;6 (6):1631-1643.
59. Parker AJ, Houston JB. Rate-limiting steps in hepatic drug clearance: comparison of hepatocellular uptake and metabolism with microsomal metabolism of saquinavir, nelfinavir, and ritonavir. Drug Metab Dispos 2008;36 (7):1375-1384.
60. Watanabe T, Kusuhara H, Maeda K, Kanamaru H, Saito Y, Hu Z, Sugiyama Y. Investigation of the rate-determining process in the hepatic elimination of HMG-CoA reductase inhibitors in rats and humans. Drug Metab Dispos 2010;38 (2):215-222.
61. Gertz M, Cartwright CM, Hobbs MJ, Kenworthy KE, Rowland M, Houston JB, Galetin A. Cyclosporine inhibition of hepatic and intestinal CYP3A4, uptake and efflux transporters: application of PBPK modeling in the assessment of drug-drug interaction potential. Pharm Res 2013;30 (3):761-780.
62. Konig J, Zolk O, Singer K, Hoffmann C, Fromm MF. Doubletransfected MDCK cells expressing human OCT1/MATE1 or OCT2/MATE1: determinants of uptake and transcellular translocation of organic cations. Br J Pharmacol 2011;163 (3):546-555.
63. Ito S, Kusuhara H, Yokochi M, Toyoshima J, Inoue K, Yuasa H, Sugiyama Y. 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 2012;340 (2):393-403.
64. Becker ML, Visser LE, van Schaik RH, Hofman A, Uitterlinden AG, Stricker BH. Genetic variation in the multidrug and toxin extrusion 1 transporter protein influences the glucose-lowering effect of metformin in patients with diabetes: a preliminary study. Diabetes 2009;58 (3):745-749.
65. Choi JH, Yee SW, Ramirez AH, Morrissey KM, Jang GH, Joski PJ, Mefford JA, Hesselson SE, Schlessinger A, Jenkins G, Castro RA, Johns SJ, Stryke D, Sali A, Ferrin TE, Witte JS, Kwok PY, Roden DM, Wilke RA, McCarty CA, Davis RL, Giacomini KM. A common 5'-UTR variant in MATE2-K is associated with poor response to metformin. Clin Pharmacol Ther 2011;90 (5):674-684.
66. Stocker SL, Morrissey KM, Yee SW, Castro RA, Xu L, Dahlin A, Ramirez AH, Roden DM, Wilke RA, McCarty CA, Davis RL, Brett CM, Giacomini KM. The effect of novel promoter variants in MATE1 and MATE2 on the pharmacokinetics and pharmacodynamics of metformin. Clin Pharmacol Ther 2013;93 (2):186-194.
67. Sato T, Masuda S, Yonezawa A, Tanihara Y, Katsura T, Inui K. Transcellular transport of organic cations in double-transfected MDCK cells expressing human organic cation transporters hOCT1/hMATE1 and hOCT2/hMATE1. Biochem Pharmacol 2008;76 (7):894-903.
68. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM. Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem 2013;56 (3):781-795.
69. Oswald S, Haenisch S, Fricke C, Sudhop T, Remmler C, Giessmann T, Jedlitschky G, Adam U, Dazert E, Warzok R, Wacke W, Cascorbi I, Kroemer HK, Weitschies W, von Bergmann K, Siegmund W. Intestinal expression of P-glycoprotein (ABCB1), multidrug resistance associated protein 2 (ABCC2), and uridine diphosphate-glucuronosyltransferase 1A1 predicts the disposition and modulates the effects of the cholesterol absorption inhibitor ezetimibe in humans. Clin Pharmacol Ther 2006;79 (3):206-217.
70. Gerloff T, Stieger B, Hagenbuch B, Madon J, Landmann L, Roth J, Hofmann AF, Meier PJ. The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. J Biol Chem 1998;273 (16):10046-10050.
71. Noe J, Stieger B, Meier PJ. Functional expression of the canalicular bile salt export pump of human liver. Gastroenterology 2002;123 (5):1659-1666.
72. Fischer S, Beuers U, Spengler U, Zwiebel FM, Koebe HG. Hepatic levels of bile acids in end-stage chronic cholestatic liver disease. Clin Chim Acta 1996;251 (2):173-186.
73. Jacquemin E. Progressive familial intrahepatic cholestasis. Clin Res Hepatol Gastroenterol 2012;36 (Suppl 1): S26-S35.
74. Morgan RE, Trauner M, van Staden CJ, Lee PH, Ramachandran B, Eschenberg M, Afshari CA, Qualls CW Jr, Lightfoot-Dunn R, Hamadeh HK. Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci 2010;118 (2):485-500.
75. Stieger B, Fattinger K, Madon J, Kullak-Ublick GA, Meier PJ. Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Gastroenterology 2000;118 (2):422-430.
76. Pauli-Magnus C, Meier PJ, Stieger B. Genetic determinants of drug-induced cholestasis and intrahepatic cholestasis of pregnancy. Semin Liver Dis 2010;30 (2):147-159.
77. Dawson S, Stahl S, Paul N, Barber J, Kenna JG. In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans. Drug Metab Dispos 2012;40 (1):130-138.
78. Delanaye P, Mariat C, Cavalier E, Maillard N, Krzesinski JM, White CA. Trimethoprim, creatinine and creatinine-based equations. Nephron Clin Pract 2011;119 (3):c187-c193; discussion c193-c184.
79. Nuernberg B, Koehnke R, Solsky M, Hoffman J, Furst DE. Biliary elimination of low-dose methotrexate in humans. Arthritis Rheum 1990;33 (6):898-902.
80. Ueda K, Kato Y, Komatsu K, Sugiyama Y. Inhibition of biliary excretion of methotrexate by probenecid in rats: quantitative prediction of interaction from in vitro data. J Pharmacol Exp Ther 2001;297 (3):1036-1043.
81. Chu X, Bleasby K, Evers R. Species differences in drug transporters and implications for translating preclinical findings to humans. Expert Opin Drug Metab Toxicol 2013;9 (3):237-252.
82. Zhao P, Zhang L, Grillo JA, Liu Q, Bullock JM, Moon YJ, Song P, Brar SS, Madabushi R, Wu TC, Booth BP, Rahman NA, Reynolds KS, Gil Berglund E, Lesko LJ, Huang SM. Applications of physiologically based pharmacokinetic (PBPK) modeling and simulation during regulatory review. Clin Pharmacol Ther 2011;89 (2):259-267.
83. Huang SM, Abernethy DR, Wang Y, Zhao P, Zineh I. The utility of modeling and simulation in drug development and regulatory review. J Pharm Sci 2013;102 (9):2912-2923.
84. Watanabe T, Kusuhara H, Maeda K, Shitara Y, Sugiyama Y. Physiologically based pharmacokinetic modeling to predict transporter-mediated clearance and distribution of pravastatin in humans. J Pharmacol Exp Ther 2009;328 (2):652-662.
85. Kuteykin-Teplyakov K, Luna-Tortos C, Ambroziak K, Loscher W. Differences in the expression of endogenous efflux transporters in MDR1-transfected versus wildtype cell lines affect P-glycoprotein mediated drug transport. Br J Pharmacol 2010;160 (6):1453-1463.
86. Noe J, Portmann R, Brun ME, Funk C. Substrate-dependent drug-drug interactions between gemfibrozil, fluvastatin and other organic anion-transporting peptide (OATP) substrates on OATP1B1, OATP2B1, and OATP1B3. Drug Metab Dispos 2007;35 (8):1308-1314.
87. Zolnerciks JK, Booth-Genthe CL, Gupta A, Harris J, Unadkat JD. Substrate- and species-dependent inhibition of P-glycoprotein-mediated transport: implications for predicting in vivo drug interactions. J Pharm Sci 2011;100 (8):3055-3061.
88. DRUGS@FDA. Available at http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed July 4, 2013.
89. Agarwal S, Chinn L, Zhang L. An overview of transporter information in package inserts of recently approved new molecular entities. Pharm Res 2013;30 (3):899-910.
90. KALYDECP Package Insert. 2014. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203188s008lbl.pdf. Accessed May 7, 2014