Journal of Pharmaceutical Investigation

  • 제38권5호
  • /
  • Pages.313-317
  • /
  • 2008
  • /
  • 2093-5552(pISSN)
  • /
  • 2093-6214(eISSN)
한국약제학회 (The Korean Society of Pharmaceutical Sciences and Technology)
권호 표지
DOI QR코드

DOI QR Code

Effects of Naringin on the Bioavailability of Etoposide in Rats

  • 발행 : 2008.10.20
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

This study investigated the effect of naringin, a flavonoid, on the bioavailability of etoposide administered orally to rats. Etoposide (6 mg/kg) was administered orally to rats alone or with naringin (1, 4 or 12 mg/kg). Compared with the control group, the co-administration of etoposide with 4 and 12 mg/kg of naringin significantly (p<0.05) increased the area under the plasma concentration-time curve (AUC) and the peak plasma concentration ($C_{max}$) of the oral etoposide. Consequently, the absolute bioavailability (AB) of etoposide in the presence (4 and 12 mg/kg) of naringin was significantly (p<0.05) increased by $9.4{\sim}10.6%$ compared with the control group (7.4%). The relative bioavailability (RB) of etoposide was increased 1.13- to 1.44-fold compared to the control group. Enhanced bioavailability of etoposide might be due to inhibition of both cytochrome P450 (CYP) 3A4 in the intestine or liver and P-glycoprotein (P-gp) transport efflux of etoposide in the intestinal membrane. This data indicate that careful consideration of the dosage for therapy with etoposide is required in a case of clinical application of the co-administration of etoposide and naringin.

키워드

참고문헌

  1. H.F. Stahelin and A. von Wartburg, The chemical and biological route from podophyllotoxin glucoside to etoposide: Ninth Cain memorial award lecture, Cancer Res., 51, 5-15 (1991)
  2. P.I. Clark and M.L. Slevin, The clinical pharmacology of etoposide and teniposide, Clin Pharmacokinet., 12, 223-252 (1987) https://doi.org/10.2165/00003088-198712040-00001
  3. A.J. Wozniak and W.E. Ross, DNA damage as a basis for 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidene-beta-D-glucopyranoside) (etoposide) cytotoxicity, Cancer Res., 43, 120-124 (1983)
  4. J.M. van Maanen, J. de Vries, D. Pappie, E. van den Akker, V.M. Lafleur, J. Retel, J. van der Greef and H.M. Pinedo, Cytochrome P-450-mediated O-demethylation: a route in the metabolic activation of etoposide (VP-16-213), Cancer Res., 47, 4658-4662 (1987)
  5. M.V. Relling, J. Nemec, E.G. Schuetz, J.D. Schuetz, F.J. Gonzalez and K.R. Korzekwa, O-demethylation of epipodophyllotoxins is catalyzed by human cytochrome P450 3A4, Mol. Pharmacol., 45, 352-358 (1994)
  6. T. Kawashiro, K. Yamashita, X.J. Zhao, E. Koyama, M. Tani, K. Chiba and T. Ishizaki, A study on the metabolism of etoposide and possible interactions with antitumor or supporting agents by human liver microsomes, J. Pharmacol. Exp. Ther., 286, 1294-1300 (1998)
  7. B.L. Leu and J.D. Huang, Inhibition of intestinal P-glycoprotein and effects on etoposide absorption, Cancer Chemother. Pharmacol., 35, 432-436 (1995) https://doi.org/10.1007/s002800050258
  8. J. Carcel-Trullols, F. Torres-Molina, A. Araico, A. Saadeddin and J.E. Peris, Effect of cyclosporine A on the tissue distribution and pharmacokinetics of etoposide, Cancer Chemother. Pharmacol., 54, 153-160 (2004)
  9. R.P. Keller, H.J. Altermatt, P. Donatsch, H. Zihlmann, J.A. Laissue and P.C. Hiestand, Pharmacologic interactions between the resistance-modifying cyclosporine SDZ PSC 833 and etoposide (VP 16-213) enhance in vivo cytostatic activity and toxicity, Int. J. Cancer., 51, 433-438 (1992) https://doi.org/10.1002/ijc.2910510316
  10. P.B. Watkins, The barrier function of CYP3A4 and P-glycoprotein in the small bowel, Adv. Drug Deliv. Rev., 27, 161-170 (1997) https://doi.org/10.1016/S0169-409X(97)00041-0
  11. V.J. Wacher, L. Salphati and L.Z. Benet, 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
  12. B. Ameer and R.A. Weintraus, Drug interactions with grapefruit juice, Clin. Pharmacokinet., 31, 103-121 (1997)
  13. D.H. Kim, E.A. Jung, I.S. Shong, J.A. Han, T.H. Kim and M.J. Han, Intestinal bacterial metabolism of flavonoids and its relation to some biological activities, Arch. Pharm. Res., 21, 17-23 (1998) https://doi.org/10.1007/BF03216747
  14. H. Takanaga, A. Ohnishi, H. Matsuo and Y. Sawada, Inhibition of vinblastine efflux mediated by P-glycoprotein by grapefruit juice components in caco-2 cells, Biol. Pharm. Bull., 21, 1062-1066 (1998) https://doi.org/10.1248/bpb.21.1062
  15. V.A. Eagling, L. Profit and D.J. Back, Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grapefruit juice components, Br. J. Clin. Pharmacol., 48, 543-552 (1999) https://doi.org/10.1046/j.1365-2125.1999.00052.x
  16. D.G. Bailey, J. Malcolm, O. Arnold and J.D. Spence, Grapefruit juice-drug interactions, Br. J. Clin. Pharmacol., 46, 101-110 (1998) https://doi.org/10.1046/j.1365-2125.1998.00764.x
  17. G.C. Kane and J.J. Lipsky, Drug-grapefruit juice interactions, Mayo. Clin. Proc., 75, 933-942 (2000)
  18. Y.C. Zhang and L.Z. Benet, The gut as a barrier to drug absorption-combined role of cytochrome P450 3A and P-glycoprotein, Clin. Pharmacokinet., 40, 159-168 (2001) https://doi.org/10.2165/00003088-200140030-00002
  19. U. Fuhr and A.L. Kummert, The fate of naringin in humans: a key to grapefruit juice-drug interactions? Clin. Pharmacol. Ther., 58, 365-373 (1995) https://doi.org/10.1016/0009-9236(95)90048-9
  20. D.G. Bailey, J.H. Kreeft, C. Munoz, D.J. Freeman and J.R. Bend, Grapefruit juice-felodipine interaction: effect of naringin and 6', 7'- dihydroxybergamottin in humans, Clin. Pharmacol. Ther., 64, 248-256 (1998) https://doi.org/10.1016/S0009-9236(98)90173-4
  21. P.C. Ho, D.J. Saville, P.F. Coville and S. Wanwimolruk, Content of CYP3A4 inhibitors, naringin, naringenin and bergapten in grapefruit and grapefruit juice products, Pharm. Acta Helv., 74, 379-385 (2000) https://doi.org/10.1016/S0031-6865(99)00062-X
  22. E. Liliemark, B. Pettersson, C. Peterson and J. Liliemark, High-performance liquid chromatography with fluorometric detection for monitoring of etoposide and its cis-isomer in plasma and leukaemic cells, J. Chromatogr. B. Biomed. Appl., 669, 311-317 (1995) https://doi.org/10.1016/0378-4347(95)00113-W
  23. K.K. Manouilov, T.R. McGuire, B.G. Gordon and P.R. Gwilt, Assay for etoposide in human serum using solid-phase extraction and high-performance liquid chromatography with fluorescence detection, J. Chromatogr. B. Biomed. Sci. Appl., 707, 342-346 (1998) https://doi.org/10.1016/S0378-4347(97)00543-4
  24. J.S. Choi and S.C. Shin, Enhanced paclitaxel bioavailability after oral coadministration of paclitaxel prodrug with naringin to rats, Int. J. Pharm., 292, 149-156 (2005) https://doi.org/10.1016/j.ijpharm.2004.11.031
  25. L. Sutherland, T. Ebner and B. Burchell, The expression of UDP-glucuronosyltransferases of the UGT1 family in human liver and kidney and in response to drugs, Biochem. Pharmacol., 45, 295-301 (1993) https://doi.org/10.1016/0006-2952(93)90064-4
  26. D. Turgeon, J.S. Carrier, E. Levesque, D.W. Hum and A. Belanger, Relative enzymatic activity, protein stability and tissue distribution of human steroid-metabolizing UGT2B subfamily members, Endocrinology., 142, 778-787 (2001) https://doi.org/10.1210/en.142.2.778
  27. S.C. Lim and J.S. Choi, Effects of naringin on the pharmacokinetics of intravenous paclitaxel in rats, Biopharm. Drug Dispos., 27, 443-447 (2006) https://doi.org/10.1002/bdd.523
  28. X. Li, J.K. Yun and J.S. Choi, Effects of morin on the pharmacokinetics of etoposide in rats, Biopharm. Drug Dispos., 28, 151-156 (2007) https://doi.org/10.1002/bdd.539