Biomolecules & Therapeutics

  • 제30권6호
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  • Pages.510-519
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  • 2022
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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Effects of Dextran Sulfate Sodium-Induced Ulcerative Colitis on the Disposition of Tofacitinib in Rats

  • Bae, Sung Hun (College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University) ;
  • Kim, Hyo Sung (College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University) ;
  • Choi, Hyeon Gyeom (College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University) ;
  • Chang, Sun-Young (College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University) ;
  • Kim, So Hee (College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University)
  • 투고 : 2022.04.14
  • 심사 : 2022.06.09
  • 발행 : 2022.11.01
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초록

Tofacitinib, a Janus kinase 1 and 3 inhibitor, is mainly metabolized by CYP3A1/2 and CYP2C11 in the liver. The drug has been approved for the chronic treatment of severe ulcerative colitis, a chronic inflammatory bowel disease. This study investigated the pharmacokinetics of tofacitinib in rats with dextran sulfate sodium (DSS)-induced ulcerative colitis. After 1-min of intravenous infusion of tofacitinib (10 mg/kg), the area under the plasma concentration-time curves from time zero to time infinity (AUC) of tofacitinib significantly increased by 92.3%. The time-averaged total body clearance decreased significantly by 47.7% in DSS rats compared with control rats. After the oral administration of tofacitinib (20 mg/kg), the AUC increased by 85.5% in DSS rats. These results could be due to decreased intrinsic clearance of the drug caused by the reduction of CYP3A1/2 and CYP2C11 in the liver and intestine of DSS rats. In conclusion, ulcerative colitis inhibited CYP3A1/2 and CYP2C11 in the liver and intestines of DSS rats and slowed the metabolism of tofacitinib, resulting in increased plasma concentrations of tofacitinib in DSS rats.

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과제정보

This work was supported by Basic Science Research Program (NRF-2021R1A2C1011142) through the National Research Foundation of Korea grant funded by the Ministry of Science and ICT, Republic of Korea.

참고문헌

  1. Ahn, C. Y., Bae, S. K., Bae, S. H., Kim, T., Jung, Y. S., Kim, Y. C., Lee, M. G. and Shin, W. G. (2009) Pharmacokinetics of oltipraz in diabetic rats with liver cirrhosis. Br. J. Pharmacol. 156, 1019-1028. https://doi.org/10.1111/j.1476-5381.2008.00105.x
  2. Bae, S. H., Chang, S. Y. and Kim, S. H. (2020) Slower elimination of tofacitinib in acute renal failure rat models: contribution of hepatic metabolism and renal excretion. Pharmaceutics 12, 714. https://doi.org/10.3390/pharmaceutics12080714
  3. Baumgart, D. C. and Carding, S. R. (2007) Inflammatory bowel disease: cause and immunobiology. Lancet 369, 1627-1640. https://doi.org/10.1016/S0140-6736(07)60750-8
  4. Bergan, T., Bjerke, P. E. and Fausa, O. (1981) Pharmacokinetics of metronidazole in patients with enteric disease compared to normal volunteers. Chemotherapy 27, 233-238. https://doi.org/10.1159/000237985
  5. Cada, D. J., Demaris, K., Levien, T. L. and Baker, D. E. (2013) Tofacitinib. Hosp. Pharm. 48, 413-424. https://doi.org/10.1310/hpj4805-413
  6. Changelian, P. S., Moshinsky, D., Kuhn, C. F., Flanagan, M. E., Munchhof, M. J., Harris, T. M., Whipple, D. A., Doty, J. L., Sun, J., Kent, C. R., Magnuson, K. S., Perregaux, D. G., Sawyer, P. S. and Kudlacz, E. M. (2008) The specificity of JAK3 kinase inhibitors. Blood 111, 2155-2157. https://doi.org/10.1182/blood-2007-09-115030
  7. Chen, C., Shah, Y. M., Morimura, K., Krausz, K. W., Miyazaki, M., Richardson, T. A., Morgan, E. T., Ntambi, J. M., Idle, J. R. and Gonzalez, F. J. (2008) Metabolomics reveals that hepatic stearoyl-CoA desaturase 1 downregulation exacerbates inflammation and acute colitis. Cell Metab. 7, 135-147. https://doi.org/10.1016/j.cmet.2007.12.003
  8. Chiou, W. L. (1978) Critical evaluation of the potential error in pharmacokinetic studies of using the linear trapezoidal rule method for the calculation of the area under the plasma level--time curve. J. Pharmacokinet. Biopharm. 6, 539-546. https://doi.org/10.1007/BF01062108
  9. Claxton, L., Taylor, M., Soonasra, A., Bourret, J. A. and Gerber, R. A. (2018) An economic evaluation of tofacitinib treatment in rheumatoid arthritis after methotrexate or after 1 or 2 TNF inhibitors from a U.S. payer perspective. J. Manag. Care Spec. Pharm. 24, 1010-1017.
  10. Daujat-Chavanieu, M. and Gerbal-Chaloin, S. (2020) Regulation of CAR and PXR expression in health and disease. Cells 9, 2395. https://doi.org/10.3390/cells9112395
  11. Dowty, M. E., Lin, J., Ryder, T. F., Wang, W., Walker, G. S., Vaz, A., Chan, G. L., Krishnaswami, S. and Prakash, C. (2014) The pharmacokinetics, metabolism and clearance mechanisms of tofacitinib, a Janus kinase inhibitor, in humans. Drug Metab. Dispos. 42, 759-773. https://doi.org/10.1124/dmd.113.054940
  12. Duggleby, R. G. (1995) Analysis of enzyme progress curves by nonlinear regression. Methods Enzymol. 249, 61-90. https://doi.org/10.1016/0076-6879(95)49031-0
  13. Fan, X., Ding, X. and Zhang, Q. Y. (2020) Hepatic and intestinal biotransformation gene expression and drug disposition in a dextran sulfate sodium-induced colitis mouse model. Acta Pharm. Sin. B. 10, 123-135. https://doi.org/10.1016/j.apsb.2019.12.002
  14. Flanagan, M. E., Blumenkopf, T. A., Brissette, W. H., Brown, M. F., Casavant, J. M., Shang-Poa, C., Doty, J. L., Elliott, E. A., Fisher, M. B., Hines, M., Kent, C., Kudlacz, E. M., Lillie, B. M., Magnuson, K. S., McCurdy, S. P., Munchhof, M. J., Perry, B. D., Sawyer, P. S., Strelevitz, T. J., Subramanyam, C., Sun, J., Whipple, D. A. and Changelian, P. S. (2010) Discovery of CP-690,550: a potent and selective Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases and organ transplant rejection. J. Med. Chem. 53, 8468-8484.
  15. Fukuda, T., Naganuma, M. and Kanai, T. (2019) Current new challenges in the management of ulcerative colitis. Intest. Res. 17, 36-44. https://doi.org/10.5217/ir.2018.00126
  16. Gao, X. J., Li, T., Wei, B., Yan, Z. X. and Yan, R. (2017) Regulatory mechanisms of gut microbiota on intestinal CYP3A and P-glycoprotein in rats with dextran sulfate sodium-induced colitis. Yao Xue Xue Bao 52, 34-43.
  17. Gibaldi, M. and Perrier, D. (1982) Pharmacokinetics, 2nd ed. Marcel-Dekker, New York.
  18. Gwak, E. H., Yoo, H. Y. and Kim, S. H. (2020) Effects of diabetes mellitus on the disposition of tofacitinib, a Janus kinase inhibitor, in rats. Biomol. Ther. (Seoul) 28, 361-369. https://doi.org/10.4062/biomolther.2020.006
  19. Hu, N., Ling, J., Dong, L., Jiang, Y., Zhou, Q. and Zou, S. (2020) Pharmacokinetics of omeprazole in rats with dextran sulfate sodium-induced ulcerative colitis. Drug Metab. Pharmacokinet. 35, 297-303. https://doi.org/10.1016/j.dmpk.2020.02.002
  20. Hussar, D. A. (2014) 2013 new drug update: what do new approvals hold for the elderly? Consult. Pharm. 29, 224-238. https://doi.org/10.4140/TCP.n.2014.224
  21. Kim, J. E., Park, M. Y. and Kim, S. H. (2020) Simple determination and quantification of tofacitinib, a JAK inhibitor, in rat plasma, urine and tissue homogenates by HPLC and its application to a pharmacokinetic study. J. Pharm. Investig. 50, 603-612. https://doi.org/10.1007/s40005-020-00490-z
  22. Kim, S. H., Lee, J. S. and Lee, M. G. (1999) Stability, blood partition and plasma protein binding of ipriflavone, an isoflavone derivative. Biopharm. Drug Dispos. 20, 355-360. https://doi.org/10.1002/(SICI)1099-081X(199910)20:7<355::AID-BDD197>3.0.CO;2-X
  23. Kumagai, M., Ishii, M., Morimoto, K. and Tomita, M. (2020) Increased membrane permeation and blood concentration of 6-carboxyfluorescein associated with dysfunction of paracellular route barrier in the small intestine of ulcerative colitis model rats. Biopharm. Drug Dispos. 41, 91-100. https://doi.org/10.1002/bdd.2220
  24. Kusunoki, Y., Kido, Y., Naito, Y., Kon, R., Mizukami, N., Kaneko, M., Wakui, N., Machida, Y. and Ikarashi, N. (2017) Changes in the pharmacokinetics of phenytoin in dextran sulfate sodium-induced ulcerative colitis in mice. Int. J. Toxicol. 36, 485-491. https://doi.org/10.1177/1091581817735987
  25. Kusunoki, Y., Ikarashi, N., Hayakawa, Y., Ishii, M., Kon, R., Ochiai, W., Machida,Y. and Sugiyama, K. (2014) Hepatic early inflammation induces downregulation of hepatic cytochrome P450 expression and metabolic activity in the dextran sulfate sodium-induced murine colitis. Eur. J. Pharm. Sci. 54, 17-27. https://doi.org/10.1016/j.ejps.2013.12.019
  26. Latteri, M., Angeloni, G., Silveri, N. G., Manna, R., Gasbarrini, G. and Navarra, P. (2001) Pharmacokinetics of cyclosporin microemulsion in patients with inflammatory bowel disease. Clin. Pharmacokinet. 40, 473-483. https://doi.org/10.2165/00003088-200140060-00006
  27. Lee, J. S. and Kim, S. H. (2019) Dose-dependent pharmacokinetics of tofacitinib in rats: Influence of hepatic and intestinal first-pass metabolism. Pharmaceutics 11, 318. https://doi.org/10.3390/pharmaceutics11070318
  28. Lee, Y. K., Chin, Y. W. and Choi, Y. H. (2013) Effects of Korean red ginseng extract on acute renal failure induced by gentamicin and pharmacokinetic changes by metformin in rats. Food Chem. Toxicol. 59, 153-159. https://doi.org/10.1016/j.fct.2013.05.025
  29. Liu, Y. F., Niu, G. C., Li, C. Y., Guo, J. B., Song, J., Li, H. and Zhang, X. L. (2021) Mechanism of ulcerative colitis-aggravated liver fibrosis: the activation of hepatic stellate cells and TLR4 signaling through gut-liver axis. Front. Physiol. 12, 695019. https://doi.org/10.3389/fphys.2021.695019
  30. Masubuchi, Y. and Horie, T. (2004) Endotoxin-mediated disturbance of hepatic cytochrome P450 function and development of endotoxin tolerance in the rat model of dextran sulfate sodium-induced experimental colitis. Drug Metab. Dispos. 32, 437-441. https://doi.org/10.1124/dmd.32.4.437
  31. Mitruka, B. M. and Rawnsley, H. M. (1981) Clinical biomedical and hematological reference values in normal experimental animals and normal humans, 2nd ed. Masson Publishing, USA Inc., New York.
  32. Mori, M., Stokes, K. Y., Vowinkel, T., Watanabe, N., Elrod, J. W., Harris, N. R., Lefer, D. J., Hibi, T. and Granger, D. N. (2005) Colonic blood flow responses in experimental colitis: time course and underlying mechanisms. Am. J. Physiol. Gastrointest. Liver Physiol. 289, G1024-G1029. https://doi.org/10.1152/ajpgi.00247.2005
  33. Okayasu, I., Hatakeyama, S., Yamada, M., Ohkusa, T., Inagaki, Y. and Nakaya, R. (1990) A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98, 694-702. https://doi.org/10.1016/0016-5085(90)90290-H
  34. Ordas, I., Eckmann, L., Talamini, M., Baumgart, D. C. and Sandborn W. J. (2012) Ulcerative colitis. Lancet 380, 1606-1619. https://doi.org/10.1016/S0140-6736(12)60150-0
  35. Park, H. J., Bae, S. H. and Kim, S. H. (2021) Dose-independent pharmacokinetics of loganin in rats: effect of intestinal first-pass metabolism on bioavailability. J. Pharm. Investig. 51, 767-776. https://doi.org/10.1007/s40005-021-00546-8
  36. Pastor Rojo, O., Lopez San Roman, A., Albeniz Arbizu, E., de la Hera Martinez, A., Ripoll Sevillano, E. and Albillos Martinez, A. (2007) Serum lipopolysaccharide-binding protein in endotoxemic patients with inflammatory bowel disease. Inflamm. Bowel Dis. 13, 269-277. https://doi.org/10.1002/ibd.20019
  37. Sandborn, W. J., Peyrin-Biroulet, L., Sharara, A. I., Su, C., Modesto, I., Mundayat, R., Gunay, L. M., Salese, L. and Sands, B. E. (2022) Efficacy and safety of tofacitinib in ulcerative colitis based on prior tumor necrosis factor inhibitor failure status. Clin. Gastroenterol. Hepatol. 20, 591-601. https://doi.org/10.1016/j.cgh.2021.02.043
  38. Sartor, R. B. (2008) Microbial influences in inflammatory bowel diseases. Gastroenterology 134, 577-594. https://doi.org/10.1053/j.gastro.2007.11.059
  39. Scott, L. J. (2013) Tofacitinib: a review of its use in adult patients with rheumatoid arthritis. Drugs 73, 857-874. https://doi.org/10.1007/s40265-013-0065-8
  40. Shin, W. G., Lee, M. G., Lee, M. H. and Kim, N. D. (1991) Factors influencing the protein binding of vancomycin. Biopharm. Drug Dispos. 12, 637-646. https://doi.org/10.1002/bdd.2510120902
  41. Solomon, L., Mansor, S., Mallon, P., Donnelly, E., Hoper, M., Loughrey, M., Kirk, S. and Gardiner, K. (2010) The dextran sulphate sodium (DSS) model of colitis: an overview. Comp. Clin. Pathol. 19, 235-239. https://doi.org/10.1007/s00580-010-0979-4
  42. Svein, O. and Theodor, W. G. (1982) Comparison of equilibrium time in dialysis experiments using spiked plasma or spiked buffer. J. Pharm. Sci. 71, 127-128. https://doi.org/10.1002/jps.2600710136
  43. Taurog, J. D., Richardson, J. A., Croft, J. T., Simmons, W. A., Zhou, M., Fernandez-Sueiro, J. L., Balish, E. and Hammer, R. E. (1994) The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J. Exp. Med. 180, 2359-2364. https://doi.org/10.1084/jem.180.6.2359
  44. Wada, T., Gao, J. and Xie, W. (2009) PXR and CAR in energy metabolism. Trends Endocrinol. Metab. 20, 273-279. https://doi.org/10.1016/j.tem.2009.03.003
  45. Yang, Y., Hu, N., Gao, X. J., Li, T., Yan, Z. X., Wang, P. P., Wei, B., Li, S., Zhang, Z. J., Li, S. L. and Yan, R. (2021) Dextran sulfate sodium-induced colitis and ginseng intervention altered oral pharmacokinetics of cyclosporine A in rats. J. Ethnopharmacol. 265, 113251. https://doi.org/10.1016/j.jep.2020.113251