Biomolecules & Therapeutics

  • 제25권5호
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  • Pages.553-558
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  • 2017
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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 Adamantyl Derivatives on Pharmacokinetic Behavior of Paclitaxel in Rats

  • Kim, Kyung Mi (Graduate School of Pharmaceutical Sciences, Ewha Womans University) ;
  • Lee, Kyeong (College of Pharmacy, Dongguk University) ;
  • Jang, Kyusic (College of Pharmacy, Dongguk University) ;
  • Moon, Yae Seul (Graduate School of Pharmaceutical Sciences, Ewha Womans University) ;
  • Lee, Hwa Jeong (Graduate School of Pharmaceutical Sciences, Ewha Womans University) ;
  • Rhie, Sandy Jeong (College of Pharmacy and Division of Life and Pharmaceutical Sciences, Ewha Womans University)
  • 투고 : 2016.08.23
  • 심사 : 2016.11.15
  • 발행 : 2017.09.01
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초록

Paclitaxel (PTX) is one of the most frequently used anticancer agent for treating refractory ovarian cancer, metastatic breast cancer and non-small cell lung cancer. However, its oral administration is impeded by very low bioavailability (<5%) due to the P-glycopprotein (P-gp) efflux pump effect. This study investigated in vitro and in vivo P-gp inhibitory effects of adamantyl derivatives AC-603 and AC-786 in rats. Two adamantyl derivatives tested in this study increased the cytotoxicity of daunomycin (DNM) in P-gp overexpressed cell line by inhibiting P-gp efflux function. Pharmacokinetics of PTX with orally co-administered P-gp inhibitors were assessed in rats to improve PTX absorption. The pharmacokinetic parameters of PTX were determined in rats after intravenous (2 mg/kg) or oral (25 mg/kg) administration in the presence or absence of verapamil (a positive control), AC-603 or AC-786 (0.5 mg/kg or 5 mg/kg). Compared to control group (PTX alone), experimental groups (PTX with AC-603 or AC-786) significantly increased the area under the plasma concentration-time curve of PTX following oral administration by 1.7-2.2 fold. The volume of distribution and total clearance of PTX were decreased, while other parameters were not significantly changed. In conclusion, co-administration of AC-603 or AC-786 enhanced the relative bioavailability of orally administered PTX as compared to control.

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참고문헌

  1. Ambudkar, S. V., Dey, S., Hrycyna, C. A., Ramachandra, M., Pastan, I. and Gottesman, M. M. (1999) Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu. Rev. Pharmacol. Toxicol. 39, 361-398. https://doi.org/10.1146/annurev.pharmtox.39.1.361
  2. Amin, M. L. (2013) P-glycoprotein inhibition for optimal drug delivery. Drug Target Insights 7, 27-34.
  3. Cai, Q., Deng, X., Li, Z., An, D., Shen, T. and Zhong, M. (2016) Effects of lipid vehicle and P-glycoprotein inhibition on the mesenteric lymphatic transport of paclitaxel in unconscious, lymph duct-cannulated rats. Drug Deliv. 23, 147-153. https://doi.org/10.3109/10717544.2014.907841
  4. Choi, J. S., Jo, B. W. and Kim, Y. C. (2004) Enhanced paclitaxel bioavailability after oral administration of paclitaxel or prodrug to rats pretreated with quercetin. Eur. J. Pharm. Biopharm. 57, 313-318. https://doi.org/10.1016/j.ejpb.2003.11.002
  5. Colin, P., De Smet, L., Vervaet, C., Remon, J. P., Ceelen, W., Van Bocxlaer, J., Boussery, K. and Vermeulen, A. (2014) A model based analysis of IPEC dosing of paclitaxel in rats. Pharm. Res. 31, 2876-2886. https://doi.org/10.1007/s11095-014-1384-5
  6. Hendrikx, J. J., Lagas, J. S., Rosing, H., Schellens, J. H., Beijnen, J. H. and Schinkel, A. H. (2013) P-glycoprotein and cytochrome P450 3A act together in restricting the oral bioavailability of paclitaxel. Int. J. Cancer 132, 2439-2447. https://doi.org/10.1002/ijc.27912
  7. Kumar, N. (1981) Taxol-induced polymerization of purified tubulin. Mechanism of action. J. Biol. Chem. 256, 10435-10441.
  8. Malingre, M. M., Schellens, J. H., Van Tellingen, O., Ouwehand, M., Bardelmeijer, H. A., Rosing, H., Koopman, F. J., Schot, M. E., Ten Bokkel Huinink, W. W. and Beijnen, J. H. (2001) The co-solvent Cremophor EL limits absorption of orally administered paclitaxel in cancer patients. Br. J. Cancer 85, 1472-1477. https://doi.org/10.1054/bjoc.2001.2118
  9. Min, K. H., Xia, Y., Kim, E. K., Jin, Y., Kaur, N., Kim, E. S., Kim, D. K., Jung, H. Y., Choi, Y., Park, M. K., Min, Y. K., Lee, K. and Lee, K. (2009) A novel class of highly potent multidrug resistance reversal agents: disubstituted adamantyl derivatives. Bioorg. Med. Chem. Lett. 19, 5376-5379. https://doi.org/10.1016/j.bmcl.2009.07.127
  10. Naik, R., Jeon, C., Min, H., Choi, H. K., Min, K. H. and Lee, K. (2011) Synthesis and bioactivity of novel adamantyl derivatives as potent MDR reversal agents. Bull. Korean Chem. Soc. 32, 4444-4446. https://doi.org/10.5012/bkcs.2011.32.12.4444
  11. Pan, Y., Hsu, V., Grimstein, M., Zhang, L., Arya, V., Sinha, V., Grillo, J.A. and Zhao, P. (2016) The application of physiologically based pharmacokinetic modeling to predict the role of drug transporters: scientific and regulatory perspectives. J. Clin. Pharmacol. 56 Suppl 7, S122-S131. https://doi.org/10.1002/jcph.740
  12. Patel, V., Kukadiya, H., Mashru, R., Surti, N. and Mandal, S. (2010) Development of microemulsion for solubility enhancement of clopidogrel. Iran. J. Pharm. Res. 9, 327-334.
  13. Sezgin-Bayindir, Z., Onay-Besikci, A., Vural, N. and Yuksel, N. (2013) Niosomes encapsulating paclitaxel for oral bioavailability enhancement:preparation, characterization, pharmacokinetics and biodistribution. J. Microencapsul. 30, 796-804. https://doi.org/10.3109/02652048.2013.788088
  14. Sparreboom, A., van Asperen, J., Mayer, U., Schinkel, A. H., Smit, J. W., Meijer, D. K., Borst, P., Nooijen, W. J., Beijnen, J. H. and van Tellingen, O. (1997) Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc. Natl. Acad. Sci. U.S.A. 94, 2031-2035. https://doi.org/10.1073/pnas.94.5.2031
  15. Theis, J. G., Liau-Chu, M., Chan, H. S., Doyle, J., Greenberg, M. L. and Koren, G. (1995) Anaphylactoid reactions in children receiving high-dose intravenous cyclosporine for reversal of tumor resistance:the causative role of improper dissolution of Cremophor EL. J. Clin. Oncol. 13, 2508-2516. https://doi.org/10.1200/JCO.1995.13.10.2508
  16. U. S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research and Center for Veterinary Medicine (2001) Guidance for industry: Bioanalytical methods validation. Available from: http://www.fda.gov/downloads/Drugs/Guidance/ucm070107.pdf/.
  17. van Zuylen, L., Verweij, J. and Sparreboom, A. (2001) Role of formulation vehicles in taxane pharmacology. Invest. New Drugs 19, 125-141. https://doi.org/10.1023/A:1010618632738
  18. Wang, T. H., Wang, H. S. and Soong, Y. K. (2000) Paclitaxel-induced cell death: where the cell cycle and apoptosis come together. Cancer 88, 2619-2628. https://doi.org/10.1002/1097-0142(20000601)88:11<2619::AID-CNCR26>3.0.CO;2-J
  19. Wang, Y., Wu, K. C., Zhao, B. X., Zhao, X., Wang, X., Chen, S., Nie, S. F., Pan, W. S., Zhang, X. and Zhang, Q. (2011) A novel paclitaxel microemulsion containing a reduced amount of Cremophor EL: pharmacokinetics, biodistribution, and in vivo antitumor efficacy and safety. J. Biomed. Biotechnol. 2011, 854872.
  20. Wu, C. P., Ohnuma, S. and Ambudkar, S. V. (2011) Discovering natural product modulators to overcome multidrug resistance in cancer chemotherapy. Curr. Pharm. Biotechnol. 12, 609-620. https://doi.org/10.2174/138920111795163887

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