Journal of Pharmaceutical Investigation

  • 제33권4호
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  • Pages.299-304
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  • 2003
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  • 2093-5552(pISSN)
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  • 2093-6214(eISSN)
한국약제학회 (The Korean Society of Pharmaceutical Sciences and Technology)
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딜티아젬과 파크리탁셀의 약물동태학적 상호작용

Pharmacokinetic Interaction between Diltiazem and Paclitaxel in Rats

  • 발행 : 2003.12.20
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초록

The purpose of this study was to investigate the effect of coadministration (2.5, 10, 20 mg/kg) and 3 or 7 days-pretreatment (10 mg/kg) of diltiazem on the pharmacokinetic parameters of paclitaxel (50 mg/kg) given orally in rats. The plasma concentrations of paclitaxel coadministered or pretreated with diltiazem were significantly (p<0.05 at 20 mg/kg coadmin., p<0.05 at pretreat.) increased compared to that of control, from 0.5 hr to 24 hr. Area under the plasma concentration-time curve (AUC) of paclitaxel coadministered or pretreated with diltiazem was significantly (p<0.05 at 20 mg/kg coadmin., p<0.01 at pretreat.) higher than that of control. Peak concentrations $(C_{max})$ of paclitaxel with diltiazem were significantly (p<0.05 at 20 mg/kg coadmn. and pretreat.) increased compared to that of control. Elimination rate constants $(K_{el})$ of paclitaxel with diltiazem were significantly (p<0.05 at 20 mg/kg and 7 days-pretreat.) reduced compared to those of control. Half-life $(t_{1/2})$ and mean residence time (MRT) of paclitaxel with diltiazem was significantly (p<0.05 at 20 mg/kg ad 7 days-pretreat.) prolonged compared to those of control. Absolute bioavailability (AB%) of paclitaxel with diltiazem was significantly (p<0.05 at 20 mg/kg and 3 days-pretreat, p<0.01 at 7 days -pretreat.) increased compared to that of control. Based on these results, it might be considered that diltiazem may inhibit cytochrome $P_{450}$ and P-glycoprotein, which are respectively engaged in paclitaxel absorption and metabolism in liver and gastrointestinal mucosa.

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참고문헌

  1. R.C. Donehower, E.K. Rowinsky and L.B. Grochow et al., Phase I trial of taxol in patients with advanced malignancies, Cancer Treat. Rep., 71, 1171-1177 (1987)
  2. S.S. Legha, D.M. Tenney and I.R. Krakhoff, Phase I study of taxol using a 5-day intermittent schedule, J. Clin. Oncol., 5, 1232-1239 (1987)
  3. A.I. Einzig, H. Hochster and P.H. Wiernik et al., A phase study of taxol in patients with malignant melanoma. Invest, New. Drugs., 9, 59-64 (1991)
  4. W.P. McGuire, E.K . Rowinsky and N.B. Rosenheim et al.,Taxol: A unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasm. Ann. Intern. Med., 111, 273-279 (1989) https://doi.org/10.7326/0003-4819-111-4-273
  5. A.I. Einzig, P.H. Wiernik and J. Sasloff et al., Phase study and long-term follow up of patients treated with taxol for advanced ovarian adenocarcinoma, J. Clin. Oncol., 10, 1748-1753 (1992) https://doi.org/10.1200/JCO.1992.10.11.1748
  6. A.I. Einzig, E. Gorowski and J. Sadloff et al., Phase trial of taxol in patients with metastatic renal cell carcinoma, Cancer Invest; 9, 133-136 (1991) https://doi.org/10.3109/07357909109044223
  7. G. Sarosy, E. Kohn and D.A Stone et al., Phase I study of taxol and granulocyte stimulation factor in patients with refractory ovarian cancer, J. Clin. Oncol., 10, 1165-1170 (1992) https://doi.org/10.1200/JCO.1992.10.7.1165
  8. P.H. Wiemik, E.L. Schwartz and A Einzig et al., Phase I trial of taxol given as a 24-hour infusion every 21 days: Responses seen in metastatic melanoma, J. Clin. Omcol., 5, 1232-1239 (1987) https://doi.org/10.1200/JCO.1987.5.8.1232
  9. J.L. Grem, K.D. Tutsch and K.L. Simon et al., Phase I study of taxol administered as a short iv infusion daily for 5days, Cancer Treat. Rep., 71, 1179-1184 (1987)
  10. E.K. Rowinsky, M.R. Gilbert and WP. McGuire et al., Sequences of taxol and cisplatin: A phase I and pharmacologic study, J. Clin. Oncol., 9, 1692-1703 (1991) https://doi.org/10.1200/JCO.1991.9.9.1692
  11. P.B. Watkins, The barrier function of CYP3A4 and Pglycoprotein in the small bowel, Adv. Drug Deliv. Rev., 27, 161-170 (1997) https://doi.org/10.1016/S0169-409X(97)00041-0
  12. V.H.Wacher, J.A. Silverman, Y. Zhang and L.Z. Benet, Role of P-glycoprotein and cytochrome P450 3A in limiting oral absorption of peptides and peptidomimetics, J. Pharm. Sci., 87, 1322-1330 (1998) https://doi.org/10.1021/js980082d
  13. K. Ito, H. Kusuhara and Y. Sugiyama, Effects of intestinal CYP3A4 and P-glycoprotein on oral drug absorptiontheoretical approach, Pharm. Res., 16, 225-231 (1999) https://doi.org/10.1023/A:1018872207437
  14. A. Rahman, K.R. Korzekwa, J. Grogan, F.J. Gonzalez and J.W. Harris, Selective biotransformation of taxol to 6-hydroxytaxol by human cytochrome P450 2C8, Cancer Res., 54, 5543-5548 (1994)
  15. D.S. Sonnichsen, Q. Liu, E.G. Schuetz.J.D. Schuetz, A. Pappo and M.V. Reiling, Variability in human cytochrome P450 paclitaxel metabolism, J. Pharmacol. Exp. Ther., 275,566-571 (1995)
  16. T. Walle, Short communication; Taxol metabolism in rat hepatocytes, Biochem. Pharmacol., 46, 1661-1664 (1993) https://doi.org/10.1016/0006-2952(93)90336-U
  17. D.S. Sonnichsen and M.V. Reiling, Clinical Pharmacokinetics of paclitaxel, Clin. Pharmacokinet., 27, 256-269 (1994) https://doi.org/10.2165/00003088-199427040-00002
  18. J.W. Harris, A. Rahman, B.R. Kim, F.P. Guengerich and J.M. Collins, Metabolism of taxol by human hepatic microsomes and liver slices: participation of cytochrome P450 3A4 and an unknown P450 enzyme, Cancer Res., 54, 4026-4031 (1994)
  19. C.H. Kleinbloesem, P. van Brummelen, J.A. van de Linde, P.J. Voogd and D.D. Breimer, Calcium chennal blockers: Kinetics and dynamics in healthy subjects, Clin. Pharmacol. Ther., 35, 742-749 (1984) https://doi.org/10.1038/clpt.1984.105
  20. E.M. Sorkin, S.P. Clissold and R.N. Brogden, Calcium chennal blockers. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in ischaemic heart disease, hypertension and related cadiovascular disorders, Drugs., 30, 182-274 (1985) https://doi.org/10.2165/00003495-198530030-00002
  21. AHFS Drug information, AFS. 1317-1324, (1998)
  22. Physicians GenRx-Drug Information, Mosby, 667-672, (1996)
  23. Drug Facts and Compararisons, Facts and Comparisons, Inc. (1999)
  24. R.F, Raspa, et at., 'Calcium channel blockers in the treatment of hypertension,' Am. Fam. Physician., 48(3), 461-470, (1993)
  25. W.H., Wilson, S.E., Bates, A. Fojo, G. Bryant, Z. Zhan, J. Regis, R.E., Wittes, E.S., Jaffe, S.M. Steinberg and Herdt, J. et al., 'Controlled trial of dexverapamil, a modulator of multidrug resistance, in lymphomas refractory to EPOCH chemo- therap.' J. Clin. Oncol., 13(8), 1995-2004, (1995) https://doi.org/10.1200/JCO.1995.13.8.1995
  26. W.H., Wilson, C. Jamis-Dow, G. Bryant, F.M., Balis, R.W, Klecker, S.E., Bates, B.A., Chabner, S.M., Steinberg, D.R. Kohler and R.E, Wittes, 'Phase I and pharmacokinetic study of the multidrug resistance modulator dexverapamil with EPOCH chemotherapy,' J. Clin. Oncol., 13(8), 1985-1994, (1995) https://doi.org/10.1200/JCO.1995.13.8.1985
  27. M. Lehnert, K. Mross, J. Schueller, B. Thuerlimann, N. Kroeger and H. Kupper, 'Phase II trial of dexverapamil and epirubicin in patients with non-responsive metastatic breast cancer,' British Journal of Cancer, 77(7), 1155-1163 (1998) https://doi.org/10.1038/bjc.1998.192
  28. R Sridhar, C. Dwivedi, J. Anderson, P.B, Baker, H.M, Sharma, P. Desai and F.N, Engineer, 'Effects of verapamil on the acute toxicity of doxorubicin in vivo,' Journal of the National Cancer Institute, 84(21), 1653-1660 (1992) https://doi.org/10.1093/jnci/84.21.1653
  29. J.K. Horton, K.N, Thimmaiah, J.A, Houghton, M.E, Horowitz and P.J. Houghton, 'Modulation by verapamil of vincristine pharmacokinetics and toxicity in mice bearing human tumor xenografts,' Biochemical Pharmacology., 38(11), 1727-1736 (1989) https://doi.org/10.1016/0006-2952(89)90405-X
  30. N. Maurin, J. Catalin, M.F. Blachon and A. Durand, Assay of paclitaxel (Taxol) in plasma and urine by High Performance Liquid Chromatogrphy, J. Chromato. B., 709, 281-288(1998) https://doi.org/10.1016/S0378-4347(98)00060-7
  31. H. Mase, M. Hiraoka and F. Suzuki, Determination of New Anticancer Drug, paclitaxel, in Biological Fluids by High Performance Liquid Chromatography, Yakugaku. Zasshi., 114, 351-355 (1994)
  32. M.L. Rocci and W.J Jusko, LAGRAN program for area and monents in pharmacokinetic analysis, Computer Program in Biomedicine., 16, 203 (1983) https://doi.org/10.1016/0010-468X(83)90082-X