Combined in vitro-in vivo approach to assess the hepatobiliary disposition of a novel oral thrombin inhibitor

Molecular Pharmaceutics

Volumn 10, Issue 11, 2013, Pages 4252-4262

  Matsson, Elin M ^a   Eriksson, Ulf G ^b   Palm, Johan E ^b   Artursson, Per ^a   Karlgren, Maria ^a   Lazorova, Lucia ^a   Brännström, Marie ^b   Ekdahl, Anja ^b   Dunér, Kristina ^b   Knutson, Lars ^c   Johansson, Susanne ^b   Schützer, Kajs Marie ^b   Lennernäs, Hans ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b ASTRAZENECA R AND D   (Sweden)

^c UPPSALA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

AZD0837; biliary clearance; direct thrombin inhibitor; drug drug interactions; ketoconazole; liver transport; transport proteins

Indexed keywords

ATECEGATRAN METOXIL; BREAST CANCER RESISTANCE PROTEIN; CYTOCHROME P450 3A4; DRUG METABOLITE; KETOCONAZOLE; MULTIDRUG RESISTANCE PROTEIN; MULTIDRUG RESISTANCE PROTEIN 2; MULTIDRUG RESISTANCE PROTEIN 3; ORGANIC CATION TRANSPORTER 1; PLACEBO;

ADULT; AREA UNDER THE CURVE; ARTICLE; BILE; BILIARY EXCRETION; BLOOD SAMPLING; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EXCRETION; DRUG METABOLISM; DUODENUM BIOPSY; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; JEJUNUM; MALE; MEMBRANE VESICLE; NORMAL HUMAN; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; PROTEIN EXPRESSION;

ADULT; AMIDINES; AZETIDINES; BILE; DRUG INTERACTIONS; HUMANS; KETOCONAZOLE; LIVER; MALE; YOUNG ADULT;

EID: 84887370936     PISSN: 15438384     EISSN: 15438392     Source Type: Journal    
DOI: 10.1021/mp400341t     Document Type: Article

References (31)

1. Lip, G. Y.; Rasmussen, L. H.; Olsson, S. B.; Jensen, E. C.; Persson, A. L.; Eriksson, U.; WaÌŠhlander, K. F. Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists Eur. Heart J. 2009, 30 (23) 2897-2907
2. Olsson, S. B.; Rasmussen, L. H.; Tveit, A.; Jensen, E.; Wessman, P.; Panfilov, S.; WaÌŠhlander, K. Safety and tolerability of an immediate-release formulation of theoral direct thrombin inhibitor AZD0837 in the prevention of stroke and systemic embolism in patients with atrial fibrillation Thromb. Haemost. 2010, 103 (3) 604-612
3. Johansson, S.; Cullberg, M.; Eriksson, U. G.; Elg, M.; Dunér, K.; Jensen, E.; Wollbratt, M.; WaÌŠhlander, K. Single-dose pharmacokinetics, pharmacodynamics and safety of AZD0837, a novel oral direct thrombin inhibitor, in young healthy male subjects Int. J. Clin. Pharmacol. Ther. 2011, 49 (4) 258-267
4. Ahrens, I.; Peter, K.; Lip, G. Y.; Bode, C. Development and clinical applications of novel oral anticoagulants. Part II. Drugs under clinical investigation Discovery Med. 2012, 13 (73) 445-450
5. Deinum, J.; Mattsson, C.; Inghardt, T.; Elg, M. Biochemical and pharmacological effects of the direct thrombin inhibitor AR-H067637 Thromb. Haemost. 2009, 101 (6) 1051-1059
6. Neve, E. P.; Nordling, A.; Andersson, T. B.; Hellman, U.; Diczfalusy, U.; Johansson, I.; Ingelman-Sundberg, M. Amidoxime reductase system containing cytochrome b5 type B (CYB5B) and MOSC2 is of importance for lipid synthesis in adipocyte mitochondria J. Biol. Chem. 2012, 287 (9) 6307-6317
7. Cullberg, M.; Eriksson, U.; Wernevik, L.; Nyström, P.; Svensson, M.; Schützer, K. M.; Nilsson, L. G.; WaÌŠhlander, K. Effect of ketoconazole and grapefruit juice on the pharmacokinetics of the oral direct thrombin inhibitor AZD0837 Basic Clin. Pharmacol. Toxicol. 2007, 101, 130:P205
8. Lown, K. S.; Bailey, D. G.; Fontana, R. J.; Janardan, S. K.; Adair, C. H.; Fortlage, L. A.; Brown, M. B.; Guo, W.; Watkins, P. B. Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression J. Clin. Invest. 1997, 99 (10) 2545-2553
9. Schmiedlin-Ren, P.; Edwards, D. J.; Fitzsimmons, M. E.; He, K.; Lown, K. S.; Woster, P. M.; Rahman, A.; Thummel, K. E.; Fisher, J. M.; Hollenberg, P. F.; Watkins, P. B. Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents. Decreased enterocyte CYP3A4 concentration and mechanism-based inactivation by furanocoumarins Drug Metab. Dispos. 1997, 25 (11) 1228-1233
10. Johansson, S.; Cullberg, M.; Ekdahl, A.; WaÌŠhlander, K.; Dunér, K.; Eriksson, U. G. Pharmacokinetics of AZD0837, a novel direct thrombin inhibitor, after oral and intravenous administration to healthy male volunteers Basic Clin. Pharmacol. Toxicol. 2009, 105, 105:TP79
11. Matsson, E. M.; Palm, J. E.; Eriksson, U. G.; Bottner, P.; Lundahl, A.; Knutson, L.; Lennernäs, H. Effects of ketoconazole on the in vivo biotransformation and hepatobiliary transport of the thrombin inhibitor AZD0837 in pigs Drug Metab. Dispos. 2011, 39 (2) 239-246
12. Bergman, E.; Forsell, P.; Tevell, A.; Persson, E. M.; Hedeland, M.; Bondesson, U.; Knutson, L.; Lennernäs, H. Biliary secretion of rosuvastatin and bile acids in humans during the absorption phase Eur. J. Pharm. Sci. 2006, 29 (3-4) 205-214
13. Matsson, E. M.; Eriksson, U. G.; Knutson, L.; Hoffmann, K. J.; Logren, U.; Fridblom, P.; Petri, N.; Lennernäs, H. Biliary excretion of ximelagatran and its metabolites and the influence of erythromycin following intraintestinal administration to healthy volunteers J. Clin. Pharmacol. 2011, 51 (5) 770-783
14. Dunér, K.; Hulthe, J.; Tranberg, M. Determination of the thrombin inhibitor AZD0837 and its metabolites in human bile using mixed mode solid phase extraction and LC-MS/MS J. Chromatogr., B 2012, 904, 29-34
15. Lohmann, C.; Gelius, B.; Danielsson, J.; Skoging-Nyberg, U.; Hollnack, E.; Dudley, A.; Wahlberg, J.; Hoogstraate, J.; Gustavsson, L. Scintillation proximity assay for measuring uptake by the human drug transporters hOCT1, hOAT3, and hOATP1B1 Anal. Biochem. 2007, 366 (2) 117-125
16. Chen, Y.; Zhang, S.; Sorani, M.; Giacomini, K. M. Transport of paraquat by human organic cation transporters and multidrug and toxic compound extrusion family J. Pharmacol. Exp. Ther. 2007, 322 (2) 695-700
17. Karlgren, M.; Vildhede, A.; Norinder, U.; Wisniewski, J. R.; Kimoto, E.; Lai, Y.; Haglund, U.; Artursson, P. Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions J. Med. Chem. 2012, 55 (10) 4740-4763
18. Karlsson, J. E.; Heddle, C.; Rozkov, A.; Rotticci-Mulder, J.; Tuvesson, O.; Hilgendorf, C.; Andersson, T. B. High-activity p-glycoprotein, multidrug resistance protein 2, and breast cancer resistance protein membrane vesicles prepared from transiently transfected human embryonic kidney 293-epstein-barr virus nuclear antigen cells Drug Metab. Dispos. 2010, 38 (4) 705-714
19. Ghibellini, G.; Leslie, E. M.; Brouwer, K. L. Methods to evaluate biliary excretion of drugs in humans: an updated review Mol. Pharmaceutics 2006, 3 (3) 198-211
20. Shaffer, E. A. Review article: control of gall-bladder motor function Aliment. Pharmacol. Ther 2000, 14 (Suppl 2) 2-8
21. Stolk, M. F.; Van Erpecum, K. J.; Peeters, T. L.; Samsom, M.; Smout, A. J.; Akkermans, L. M.; Vanberge-Henegouwen, G. P. Interdigestive gallbladder emptying, antroduodenal motility, and motilin release patterns are altered in cholesterol gallstone patients Dig. Dis. Sci. 2001, 46 (6) 1328-1334
22. Stolk, M. F.; van Erpecum, K. J.; Smout, A. J.; Akkermans, L. M.; Jansen, J. B.; Lamers, C. B.; Peeters, T. L.; van Berge-Henegouwen, G. P. Motor cycles with phase III in antrum are associated with high motilin levels and prolonged gallbladder emptying Am. J. Physiol. 1993, 264 (4 Pt 1) G596-600
23. Giacomini, K. M.; Huang, S. M.; Tweedie, D. J.; Benet, L. Z.; Brouwer, K. L.; Chu, X.; Dahlin, A.; Evers, R.; Fischer, V.; Hillgren, K. M.; Hoffmaster, K. A.; Ishikawa, T.; Keppler, D.; Kim, R. B.; Lee, C. A.; Niemi, M.; Polli, J. W.; Sugiyama, Y.; Swaan, P. W.; Ware, J. A.; Wright, S. H.; Yee, S. W.; Zamek-Gliszczynski, M. J.; Zhang, L. Membrane transporters in drug development Nat. Rev. Drug Discovery 2010, 9 (3) 215-36
24. Bjornsson, T. D.; Callaghan, J. T.; Einolf, H. J.; Fischer, V.; Gan, L.; Grimm, S.; Kao, J.; King, S. P.; Miwa, G.; Ni, L.; Kumar, G.; McLeod, J.; Obach, R. S.; Roberts, S.; Roe, A.; Shah, A.; Snikeris, F.; Sullivan, J. T.; Tweedie, D.; Vega, J. M.; Walsh, J.; Wrighton, S. A. The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective Drug Metab. Dispos. 2003, 31 (7) 815-832
25. Olkkola, K. T.; Backman, J. T.; Neuvonen, P. J. Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole Clin. Pharmacol. Ther. 1994, 55 (5) 481-485
26. Chien, J. Y.; Lucksiri, A.; Ernest, C. S., II; Gorski, J. C.; Wrighton, S. A.; Hall, S. D. Stochastic prediction of CYP3A-mediated inhibition of midazolam clearance by ketoconazole Drug Metab. Dispos. 2006, 34 (7) 1208-1219
27. Zhao, P.; Ragueneau-Majlessi, I.; Zhang, L.; Strong, J. M.; Reynolds, K. S.; Levy, R. H.; Thummel, K. E.; Huang, S. M. Quantitative evaluation of pharmacokinetic inhibition of CYP3A substrates by ketoconazole: a simulation study J. Clin. Pharmacol. 2009, 49 (3) 351-359
28. Wang, E. J.; Lew, K.; Casciano, C. N.; Clement, R. P.; Johnson, W. W. Interaction of common azole antifungals with P glycoprotein Antimicrob. Agents Chemother. 2002, 46 (1) 160-165
29. Kim, R. B.; Wandel, C.; Leake, B.; Cvetkovic, M.; Fromm, M. F.; Dempsey, P. J.; Roden, M. M.; Belas, F.; Chaudhary, A. K.; Roden, D. M.; Wood, A. J.; Wilkinson, G. R. Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein Pharm. Res. 1999, 16 (3) 408-414
30. Marcelin-Jimenez, G.; Hernandez, J.; Angeles, A. P.; Contreras, L.; Hinojosa, M.; Rivera, L.; Martinez-Rossier, L.; Amancio, O.; Fernandez, A. Bioequivalence evaluation of two brands of ketoconazole tablets (Onofin-K and Nizoral) in a healthy female Mexican population Biopharm. Drug Dispos. 2004, 25 (5) 203-209
31. Ahlin, G.; Chen, L.; Lazorova, L.; Chen, Y.; Ianculescu, A. G.; Davis, R. L.; Giacomini, K. M.; Artursson, P. Genotype-dependent effects of inhibitors of the organic cation transporter, OCT1: predictions of metformin interactions Pharmacogenom. J. 2011, 11 (6) 400-411