Evaluation of cynomolgus monkeys for the identification of endogenous biomarkers for hepatic transporter inhibition and as a translatable model to predict pharmacokinetic interactions with statins in humans

Drug Metabolism and Disposition

Volumn 43, Issue 6, 2015, Pages 851-863

  Chu, Xiaoyan ^a   Shih, Shian Jiun ^b   Shaw, Rachel ^b   Hentze, Hannes ^b   Chan, Grace H ^a   Owens, Karen ^a   Wang, Shubing ^a   Cai, Xiaoxin ^a   Newton, Deborah ^a   Castro Perez, Jose ^a   Salituro, Gino ^a   Palamanda, Jairam ^a   Fernandis, Aaron ^b   Ng, Choon Keow ^b   Liaw, Andy ^a   Savage, Mary J ^a   Evers, Raymond ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b IMCB A STAR   (Singapore)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; ATORVASTATIN; BILIRUBIN; CREATINE KINASE; GLUCURONOSYLTRANSFERASE 1A1; LACTATE DEHYDROGENASE; LIOTHYRONINE; MULTIDRUG RESISTANCE ASSOCIATED PROTEIN 2; NICARDIPINE; ORGANIC ANION TRANSPORTER B; RIFAMPICIN; ROSUVASTATIN; SODIUM BILE ACID COTRANSPORTER; SOLUTE CARRIER ORGANIC ANION TRANSPORTER 1B1; SOLUTE CARRIER ORGANIC ANION TRANSPORTER 1B3; THYROXINE; AGENTS AFFECTING WATER, MOLECULE OR ION TRANSPORT; BILIRUBIN GLUCURONATE; BIOLOGICAL MARKER; CYTOCHROME P450 INDUCER; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ISOPROTEIN; ORGANIC ANION TRANSPORTER; RECOMBINANT PROTEIN;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANIMAL CELL; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BILIRUBIN BLOOD LEVEL; CONTROLLED STUDY; CREATINE KINASE BLOOD LEVEL; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG ELIMINATION; DRUG HALF LIFE; DRUG POTENCY; DRUG POTENTIATION; DRUG UPTAKE; HUMAN; HUMAN CELL; IC50; IN VITRO STUDY; IN VIVO STUDY; LACTATE DEHYDROGENASE BLOOD LEVEL; LIOTHYRONINE BLOOD LEVEL; MACACA FASCICULARIS; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PRIORITY JOURNAL; THYROXINE BLOOD LEVEL; TIME TO MAXIMUM PLASMA CONCENTRATION; ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOLOGICAL MODEL; BLOOD; CHEMISTRY; DRUG EFFECTS; DRUG INTERACTION; DRUG SCREENING; ENZYMOLOGY; EVALUATION STUDY; GENETICS; HEK293 CELL LINE; INTRAVENOUS DRUG ADMINISTRATION; LIVER MICROSOME; METABOLIC CLEARANCE RATE; METABOLISM; ORAL DRUG ADMINISTRATION; RANDOMIZATION; SPECIES DIFFERENCE;

AMBYSTOMA TIGRINUM STEBBENSI VIRUS; MACACA FASCICULARIS; RICE STRIPE VIRUS;

ADMINISTRATION, ORAL; ANIMALS; BILIRUBIN; BIOMARKERS; CYTOCHROME P-450 ENZYME INDUCERS; DRUG EVALUATION, PRECLINICAL; DRUG INTERACTIONS; HEK293 CELLS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; INJECTIONS, INTRAVENOUS; MACACA FASCICULARIS; MALE; MEMBRANE TRANSPORT MODULATORS; METABOLIC CLEARANCE RATE; MICROSOMES, LIVER; MODELS, BIOLOGICAL; ORGANIC ANION TRANSPORTERS; PROTEIN ISOFORMS; RANDOM ALLOCATION; RECOMBINANT PROTEINS; SPECIES SPECIFICITY;

EID: 84940369861     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.115.063347     Document Type: Article

References (47)

1. Campbell SD, de Morais SM, and Xu JJ (2004) Inhibition of human organic anion transporting polypeptide OATP 1B1 as a mechanism of drug-induced hyperbilirubinemia. Chem Biol Interact 150:179-187.
2. Castro-Perez J.M., Roddy TP, Shah V, Wang S.P., Ouyang X., Ogawa A, McLaren DG, Tadin-Strapps M, Robinson M.J., and Bartz SR, et al. (2011) Attenuation of Slc27a5 gene expression followed by LC-MS measurement of bile acid reconjugation using metabolomics and a stable isotope tracer strategy. J Proteome Res 10:4683-4691.
3. Center for Drug Evaluation and Research (CDER) (2003) Drug Approval Package: Crestor (rosuvastatin calcium) tablets, Company: Astra Zeneca Pharmaceuticals, Application No.: 021366, Approval Date: 8/13/2003, Pharmacology Review(s), Part 2, p. 29, U.S. Food and Drug Administration, Rockville, MD, http://www.accessdata.fda.gov/drugsatfda-docs/nda/2003/21-366-Crestor.cfm.
4. Center for Drug Evaluation and Research (CDER) (2012) Guidance for Industry: Drug Interaction Studies - Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations [Draft Guidance], U.S. Department of Health and Human Services, Food and Drug Administration, Rockville, MD. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm292362.pdf.
5. Chang JH, Plise E, Cheong J., Ho Q, and Lin M (2013) Evaluating the in vitro inhibition of UGT1A1, OATP1B1, OATP1B3, MRP2, and BSEP in predicting drug-induced hyper-bilirubinemia. Mol Pharm 10:3067-3075.
6. Chiou WJ, de Morais SM, Kikuchi R, Voorman RL, Li X, and Bow DA (2014) In vitro OATP1B1 and OATP1B3 inhibition is associated with observations of benign clinical un-conjugated hyperbilirubinemia. Xenobiotica 44:276-282.
7. Chu X, Bleasby K, and Evers R (2013a) Species differences in drug transporters and implications for translating preclinical findings to humans. Expert Opin Drug Metab Toxicol 9:237-252.
8. Chu X, Korzekwa K, Elsby R., Fenner K, Galetin A, Lai Y., Matsson P, Moss A, Nagar S., and Rosania GR, et al.; International Transporter Consortium (2013b) Intracellular drug concentrations and transporters: measurement, modeling, and implications for the liver. Clin Pharmacol Ther 94:126-141.
9. Chu XY, Huskey SE, Braun M.P., Sarkadi B., Evans DC, and Evers R (2004) Transport of ethinylestradiol glucuronide and ethinylestradiol sulfate by the multidrug resistance proteins MRP1, MRP2, and MRP3. J Pharmacol Exp Ther 309:156-164.
10. Committee for Human Medicinal Products (CHMP) (2012) Guideline on the Investigation of Drug Interactions [Final], European Medicines Agency, London. http://www.ema.europa.eu/docs/en-GB/document-library/Scientific-guideline/2012/07/WC500129606.pdf.
11. Corsini A and Bortolini M (2013) Drug-induced liver injury: the role of drug metabolism and transport. J Clin Pharmacol 53:463-474.
12. Giacomini KM, Huang SM, Tweedie D.J., Benet LZ, Brouwer KL, Chu X, Dahlin A., Evers R, Fischer V, and Hillgren KM, et al.; International Transporter Consortium (2010) Membrane transporters in drug development. Nat Rev Drug Discov 9:215-236.
13. Hagenbuch B and Stieger B (2013) The SLCO (former SLC21) superfamily of transporters. Mol Aspects Med 34:396-412.
14. He YJ, Zhang W, Chen Y., Guo D, Tu JH, Xu L.Y., Tan ZR, Chen BL, Li Z, and Zhou G, et al. (2009) Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T.C polymorphism. Clin Chim Acta 405:49-52.
15. Hirano M, Maeda K, Shitara Y., and Sugiyama Y (2006) Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab Dispos 34:1229-1236.
16. Hosea NA, Collard WT, Cole S, Maurer T.S., Fang RX, Jones H, Kakar SM, Nakai Y, Smith B.J., and Webster R, et al. (2009) Prediction of human pharmacokinetics from preclinical information: comparative accuracy of quantitative prediction approaches. J Clin Pharmacol 49:513-533.
17. Imamura Y, Tsuruya Y, Damme K., Heer D, Kumagai Y, Maeda K., Murayama N, Okudaira N, Kurihara A., and Izumi T, et al. (2014) 6b-Hydroxycortisol is an endogenous probe for evaluation of drug-drug interactions involving a multispecific renal organic anion transporter, OAT3/SLC22A8, in healthy subjects. Drug Metab Dispos 42:685-694.
18. Ito S, Kusuhara H, Kumagai Y., Moriyama Y, Inoue K, Kondo T., Nakayama H, Horita S, Tanabe K., and Yuasa H, et al. (2012) N-methylnicotinamide is an endogenous probe for evaluation of drug-drug interactions involving multidrug and toxin extrusions (MATE1 and MATE2-K). Clin Pharmacol Ther 92:635-641.
19. Izumi S, Nozaki Y, Komori T., Maeda K, Takenaka O, Kusano K., Yoshimura T, Kusuhara H and Sugiyama Y (2013) Substrate-dependent inhibition of organic anion transporting poly-peptide 1B1: comparative analysis with prototypical probe substrates estradiol-17beta-glucuronide, estrone-3-sulfate, and sulfobromophthalein. Drug Metab Dispos 41:1859-1866.
20. Jamei M, Bajot F, Neuhoff S., Barter Z, Yang J, Rostami-Hodjegan A, and Rowland-Yeo K (2014) A mechanistic framework for in vitro-in vivo extrapolation of liver membrane transporters: prediction of drug-drug interaction between rosuvastatin and cyclosporine. Clin Pharmacokinet 53:73-87.
21. Jones HM, Barton HA, Lai Y, Bi Y.A., Kimoto E., Kempshall S, Tate SC, El-Kattan A, Houston J.B., and Galetin A, et al. (2012) Mechanistic pharmacokinetic modeling for the prediction of transporter-mediated disposition in humans from sandwich culture human hepatocyte data. Drug Metab Dispos 40:1007-1017.
22. Kato K, Mori H, Kito T., Yokochi M, Ito S, Inoue K., Yonezawa A, Katsura T, Kumagai Y., and Yuasa H, et al. (2014) Investigation of endogenous compounds for assessing the drug interactions in the urinary excretion involving multidrug and toxin extrusion proteins. Pharm Res 31:136-147.
23. Keppler D (2014) The roles of MRP2, MRP3, OATP1B1, and OATP1B3 in conjugated hyper-bilirubinemia. Drug Metab Dispos 42:561-565.
24. Kim CY, Han JS, Suzuki T, and Han SS (2005) Indirect indicator of transport stress in hema-tological values in newly acquired cynomolgus monkeys. J Med Primatol 34:188-192.
25. Lau YY, Huang Y, Frassetto L., and Benet LZ (2007) effect of OATP1B transporter inhibition on the pharmacokinetics of atorvastatin in healthy volunteers. Clin Pharmacol Ther 81:194-204.
26. Lennernäs H (2003) Clinical pharmacokinetics of atorvastatin. Clin Pharmacokinet 42:1141-1160.
27. Maeda K, Ikeda Y, Fujita T., Yoshida K, Azuma Y, Haruyama Y., Yamane N, Kumagai Y, and Sugiyama Y (2011) Identification of the rate-determining process in the hepatic clearance of atorvastatin in a clinical cassette microdosing study. Clin Pharmacol Ther 90:575-581.
28. Martignoni M, Groothuis GM, and de Kanter R (2006) Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opin Drug Metab Toxicol 2:875-894.
29. Martin PD, Warwick MJ, Dane A.L., Hill SJ, Giles PB, Phillips PJ, and Lenz E (2003) Metabolism, excretion, and pharmacokinetics of rosuvastatin in healthy adult male volunteers. Clin Ther 25:2822-2835.
30. Meyer zu Schwabedissen HE, Ware JA, Finkelstein D, Chaudhry A.S., Mansell S., Leon-Ponte M, Strom SC, Zaher H, Schwarz U.I., and Freeman DJ, et al. (2011) Hepatic organic anion transporting polypeptide transporter and thyroid hormone receptor interplay determines cholesterol and glucose homeostasis. Hepatology 54:644-654.
31. Niemi M, Pasanen MK, and Neuvonen PJ (2011) Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev 63:157-181.
32. Pfeifer ND, Hardwick RN, and Brouwer KL (2014) Role of hepatic efflux transporters in regulating systemic and hepatocyte exposure to xenobiotics. Annu Rev Pharmacol Toxicol 54:509-535.
33. Pinheiro JC and Baes DM (2004) Mixed-Effects Models in S and S-PLUS, pp 27-52, Springer, New York.
34. Prueksaritanont T, Chu X, Evers R., Klopfer SO, Caro L, Kothare PA, Dempsey C, Rasmussen S., Houle R, and Chan G, et al. (2014) Pitavastatin is a more sensitive and selective organic anion-transporting polypeptide 1B clinical probe than rosuvastatin. Br J Clin Pharmacol 78:587-598.
35. Rodrigues AD, Lai Y, Cvijic M.E., Elkin LL, Zvyaga T, and Soars MG (2014) Drug-induced perturbations of the bile acid pool, cholestasis, and hepatotoxicity: mechanistic considerations beyond the direct inhibition of the bile salt export pump. Drug Metab Dispos 42:566-574.
36. Sanna S, Busonero F, Maschio A., McArdle PF, Usala G, Dei M, Lai S., Mulas A, Piras MG, and Perseu L, et al. (2009) Common variants in the SLCO1B3 locus are associated with bilirubin levels and unconjugated hyperbilirubinemia. Hum Mol Genet 18:2711-2718.
37. Shen H, Yang Z, Mintier G., Han YH, Chen C, Balimane P, Jemal M., Zhao W, Zhang R, and Kallipatti S, et al. (2013) Cynomolgus monkey as a potential model to assess drug interactions involving hepatic organic anion transporting polypeptides: in vitro, in vivo, and in vitro-to-in vivo extrapolation. J Pharmacol Exp Ther 344:673-685.
38. Takahashi T, Ohtsuka T, Yoshikawa T., Tatekawa I, Uno Y, Utoh M., Yamazaki H, and Kume T (2013) Pitavastatin as an in vivo probe for studying hepatic organic anion transporting polypeptide-mediated drug-drug interactions in cynomolgus monkeys. Drug Metab Dispos 41: 1875-1882.
39. van de Steeg E, Stránecký V, Hartmannová H, Nosková L, Hrebícek M, Wagenaar E, van Esch A, de Waart DR, Oude Elferink RP, and Kenworthy KE, et al. (2012) Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. J Clin Invest 122:519-528.
40. Vavricka SR, Van Montfoort J, Ha HR, Meier P.J., and Fattinger K (2002) Interactions of rifa-mycin SV and rifampicin with organic anion uptake systems of human liver. Hepatology 36: 164-172.
41. Vildhede A, Karlgren M, Svedberg E.K., Wisniewski JR, Lai Y, Norén A, and Artursson P (2014) Hepatic uptake of atorvastatin: influence of variability in transporter expression on uptake clearance and drug-drug interactions. Drug Metab Dispos 42:1210-1218.
42. Wang L, Prasad B, Salphati L., Chu X, Gupta A, Hop C.E., Evers R., and Unadkat JD (2015) Interspecies variability in expression of hepatobiliary transporters across human, dog, monkey, and rat as determined by quantitative proteomics. Drug Metab Dispos 43:367-374.
43. Xiang X, Backman JT, Neuvonen P.J., and Niemi M (2012) Gender, but not CYP7A1 or SLCO1B1 polymorphism, affects the fasting plasma concentrations of bile acids in human beings. Basic Clin Pharmacol Toxicol 110:245-252.
44. Xiang X, Han Y, Neuvonen M., Pasanen MK, Kalliokoski A, Backman JT, Laitila J, Neuvonen P.J., and Niemi M (2009) Effect of SLCO1B1 polymorphism on the plasma concentrations of bile acids and bile acid synthesis marker in humans. Pharmacogenet Genomics 19:447-457.
45. Yabe Y, Galetin A, and Houston JB (2011) Kinetic characterization of rat hepatic uptake of 16 actively transported drugs. Drug Metab Dispos 39:1808-1814.
46. Yoshida K, Maeda K, and Sugiyama Y (2012) Transporter-mediated drug - drug interactions involving OATP substrates: predictions based on in vitro inhibition studies. Clin Pharmacol Ther 91:1053-1064.
47. Zhang W, He YJ, Gan Z, Fan L., Li Q, Wang A, Liu Z.Q., Deng S., Huang YF, and Xu LY, et al. (2007) OATP1B1 polymorphism is a major determinant of serum bilirubin level but not associated with rifampicin-mediated bilirubin elevation. Clin Exp Pharmacol Physiol 34: 1240-1244.