Archives of Pharmacal Research

  • 제29권4호
  • /
  • Pages.333-338
  • /
  • 2006
  • /
  • 0253-6269(pISSN)
  • /
  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

Enhanced Nimodipine Bioavailability After Oral Administration of Nimodipine with Morin, a Flavonoid, in Rabbits

  • 발행 : 2006.04.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

The aim of this study was to investigate the effect of morin on the bioavailability of nimodipine after administering nimodipine (15 mg/kg) orally to rabbits either co-administered or pretreated with morin (2, 10 and 20 mg/kg). The plasma concentrations of nimodipine in the rabbits pretreated with morin were increased significantly (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg) compared with the control, but the plasma concentrations of nimodipine co-administered with morin were not significant. The areas under the plasma concentration-time curve (AUC) and the peak concentrations $(C_{max})$ of the nimodipine in the rabbits pretreated with morin were significantly higher (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg), but only the $C_{max}$ of nimodipine coadministered with morin 10 mg/kg was increased significantly (p<0.05). The absolute bioavailability $(A.B\%)$ of nimodipine in the rabbits pretreated with morin was significantly (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg) higher $(54.1-65.0\%)$ than the control $(36.7\%)$. The increased bioavailability of nimodipine in the rabbits pretreated with morin might have been resulted from the morin, which inhibits the efflux pump P-glycoprotein and the first-pass metabolizing enzyme by cytochrome P-450 3A4 (CYP 3A4).

키워드

참고문헌

  1. Choi, H. J. and Choi, J. S., Effects of morin pretreatment on the pharmacokinetics of diltiazem and its major metabolite, desacetyldiltiazem in rats. Arch. Pharm. Res., 28, 970-976 (2005a) https://doi.org/10.1007/BF02973885
  2. Choi, J. S. and Han, H. K., Pharmacokinetic interaction between diltiazem and morin, a flavonoid, in rats. Pharmacol. Res., 52, 386-391 (2005b) https://doi.org/10.1016/j.phrs.2005.05.011
  3. Dixon, R. A., and Steele, C. L., Flavonoids and isoflavonoids - a gold mine for metabolic engineering. Trends Plant Sci., 4, 394-400 (1999) https://doi.org/10.1016/S1360-1385(99)01471-5
  4. Epstein, M. and Loutzenhister, R. D., Effects of calcium antagonists on renal hemodynamics, Am. J. Kidney Dis., 16, 10-14 (1990)
  5. Fang, S. H., Hou, Y. C., Chang, W. C., Hsiu, S. L., Chao, P. D. L., and Chiang, B. L., Morin sulfates glucuronides exert antiinflammatory activity on activated macrophages and decreased the incidence of septic shock. Life Sci. 74, 743- 756 (2003) https://doi.org/10.1016/j.lfs.2003.07.017
  6. Francis, A. R., Shetty, T. K., and Bhattacharya, R. K., Modulating effect of plant flavonoids on the mutagenicity of N-methyl-N-nitro-N-nitrosoguanidine. Carcinogenesis, 10, 1953-1955 (1989) https://doi.org/10.1093/carcin/10.10.1953
  7. Gan, L. L., Moseley, M. A., Khosla, B., Augustijns, P. F., Bradshaw, T. P., Hendren, R. W., and Thakker, D. R., CYP3A-Like cytochrome P450-mediated metabolism and polarized efflux of cyclosporin A in Caco-2 cells: interaction between the two biochemical barriers to intestinal transport. Drug Metab. Dispos., 24, 344-349 (1996)
  8. Gottesman, M. M. and Pastan, I., Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu. Rev. Biochem., 62, 385-427 (1993) https://doi.org/10.1146/annurev.bi.62.070193.002125
  9. Guengerich, F. P., Brian, W. R., Iwasaki, M., Sari, M. A., Baarnhielm, C., and Berntssom, P., Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrom P-450 3A4, J. Med. Chem., 34, 1834-1844 (1991)
  10. Hanasaki, Y., Ogawa, S., and Fukui,S., The correlation between active oxygens scavenging and antioxidative effects of flavonoids. Free Radic. Biol. Med. 16, 845-850 (1994) https://doi.org/10.1016/0891-5849(94)90202-X
  11. Hodek, P., Trefil, P., and Stiborova, M., Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450. Chem. Biol. Interact., 139, 1-21 (2002) https://doi.org/10.1016/S0009-2797(01)00285-X
  12. Hsiu, S. L., Hou, Y. C., Wang, Y. H., Tsao, C. W., Su, S. F., and Chao, P. D., Quercetin significantly decreased cyclosporin oral bioavailability in pigs and rats. Life Sci., 72, 227-235 (2002) https://doi.org/10.1016/S0024-3205(02)02235-X
  13. Ito, K., Kusuhara, H., and Sugiyama, Y., Effects of intestinal CYP3A4 and P-glycoprotein on oral drug absorption theoretical approach. Pharm. Res., 16, 225-231 (1999) https://doi.org/10.1023/A:1018872207437
  14. Kazda, S., Garthoff, B., Krause, H. P., and Schlossmann, K., Cerebrovascular effects of the calcium antagonistic dihydropyridine derivative nimodipine in animal experiments, Arzneimittelforschung., 32, 331-338 (1982)
  15. Maruhn, D., Siefert, H. M., Weber, H., Ramsch, K., and Suwelack, D., Pharmacokinetics of nimodipine. communication: absorption, concentration in plasma and excretion after single administration of nimodipine in rat, dog and monkey, Arzneimittelforschung., 35, 1781-1786 (1985)
  16. Nguyen, H., Zhang, S., and Morris, M. E., Effect of flavonoids on MRP1-mediated transport in Panc-1 cells. J. Pharm. Sci., 92, 250-257 (2003) https://doi.org/10.1002/jps.10283
  17. Qian, M., and Gallo, J. M., High-perfomance liquod chromatographic determinination of the calcium channel blocker nimodipine in monkey plasma, J. Chromatogr., 578, 316-320 (1992) https://doi.org/10.1016/0378-4347(92)80432-P
  18. Ramsch, K. D., Ahr, G., Tettenborn, D., and Auer, L. M., Overview on pharmacokinetics of nimodipine in healthy volunteer and in patients with subarachnoid hemorrhage, Neurochirurgia., 28, 74-78 (1985)
  19. Rocci, M. L. and Jusko, W. J., LAGRAN program for area and moments in pharmacokinetic analysis, Computer Programs in Biomedicine, 16, 203-209 (1983) https://doi.org/10.1016/0010-468X(83)90082-X
  20. Saeki, T., Ueda, K., Tanigawara, Y., Hori, R., and Komano, T., Pglycoprotein- mediated transcellular transport of MDRreversing agents. FEBS Lett., 324, 99-102 (1993) https://doi.org/10.1016/0014-5793(93)81540-G
  21. Scherling, D., Buhner, K., Krause, H. P., Karl, W., and Wunsche, C., Biotransformation of nimodipine in rat, dog and monkey, Arzneimittelforschung., 41, 392-398 (1991)
  22. Scholz, H., Pharmacological aspects of calcium channel blockers, Cardiovasc. Drugs Ther., 10, 869-872 (1997) https://doi.org/10.1007/BF00051613
  23. Suwelack, D., Weber, H., and Maruhn, D., Pharmacokinetics of nimodipine, communication: absorption, concentration in plasma and excretion after single administration of [$^{14}$C] nimodipine in rat, dog and monkey, Arzneimittelforschung., 35, 1787-1794 (1985)
  24. Wacher, V. H., Silverman, J. A., Zhang, Y., and Benet, L Z., 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
  25. Wacher, V. J., Salphati, L., and Benet, L. Z., Active secretion and enterocytic drug metabolism barriers to drug absorption. Adv. Drug Deliv. Rev., 46, 89-102 (2001) https://doi.org/10.1016/S0169-409X(00)00126-5
  26. Watkins, P. B., The barrier function of CYP3A4 and Pglycoprotein in the small bowel. Adv. Drug Deliv. Rev., 27, 161-170 (1996) https://doi.org/10.1016/S0169-409X(97)00041-0
  27. Zhang, S. and Morris, M. E., Effects of the flavonoids biochanin A, morin, phloretin, and silymarin on P-glycoprotein-mediated transport. J. Pharmacol. Exp. Ther., 304, 1258-1267 (2003) https://doi.org/10.1124/jpet.102.044412