Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
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Pharmacokinetic Interaction between Verapamil and Quercetin in Rabbits

베라파밀과 퀠세틴의 토끼에서의 약물동태학적 상호작용

  • Published : 2004.02.20
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Abstract

The pharmacokinetics of orally administered verapamil (10 mg/kg) was studied in six rabbits after 20 min pretreatment with quercetin ad coadministration of quercetin (2.0 mg/kg, 1 mg/g and 20 mg/kg, respectively). Pretreatment with quercetin significantly (p < 0.01, p < 0.05) increased the plasma concentration of verapamil. However, coadministration of quercetin showed no significantly effect on the pharmacokinetic parameters of verapamil. The elimination rate constant $(K_{el})$ of verapamil pretreated with quercetin (1 mg/kg and 20 mg/kg) was significantly (p < 0.05) reduced compared with control. The area under the plasma concentration-time curve (AUC) and the peak concentration $(C_{max})$ of verapamil pretreated with quercetin (2.0 mg/kg, 10 mg/kg and 20 mg/kg) were increased significantly (p < 0.01, p < 0.05) compared with control. Pretreatment with quercetin (2.0 mg/kg, 10 mg/kg and 20 mg/kg) significantly (p < 0.01, p < 0.05) increased the relative bioavailability of verapamil to 159 - 219%. These results suggest that quercetin alters disposition of verapamil by inhibition of P-glycoprotein efflux pump and its first-pass metabolism. The dosage of verapamil should be adjusted when it is administered chronically with quercetin in a clinical situation.

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References

  1. A. Fleckenstein, Specific pharmacology of calcium in myo-cardium. cardiac pacemakers, and vascular smooth muscle. Annual Review of Pharmacology and Toxicology, 17, 149-166 (1977) https://doi.org/10.1146/annurev.pa.17.040177.001053
  2. D.M. Krikler and RAl Spurrel, verapamil in the treatment of paroxysmal supraventricular tachycardias. Postgraduate Medicine., 50, 447-453 (1974) https://doi.org/10.1136/pgmj.50.585.447
  3. B.A Gould, S. Mann, H. Kieso, Y. Bala Subramanian and E.B. Raftery, The 24-hour ambulatory blood pressure profile with verapamiI. Circulation., 65, 22-27 (1982) https://doi.org/10.1161/01.CIR.65.1.22
  4. G.R.J. Lewis, KD. Morley, B.M. Lewis and P.l Bones, The treatment of hypertension with verapamil. N.Z. Medical Journal, 87, 351-354 (1978)
  5. M. Schomerus, B. Spiegelhaider, B. Stieren and M. Eichelbaum, Physiologic disposition of verapamil in man. Cardiovascular Research, 10, 605-612 (1976) https://doi.org/10.1093/cvr/10.5.605
  6. G. Neugebauer, Comparative cardiovascular actions of verapamil and its major metabolites in the anesthetized dog. Cardiovascular Research, 12, 247-254 (1978) https://doi.org/10.1093/cvr/12.4.247
  7. M. Eichelbaum. E.G. Remberg, M. Schomerus and H.J. Dengler, The metabolism of $D,L(^{14}C)$ verapamil in man. Drug Metabolism and Disposition, 7, 145-148 (1979)
  8. M. Eichelbaum, G. Mikus and B. Vogelgesang, Pharmacokinetics of (+)-, (-)- and $(\pm)-verapamil$ after intravenous administration. British Journal of Clinical Pharmacology, 17, 453-458 (1984) https://doi.org/10.1111/j.1365-2125.1984.tb02371.x
  9. B.G. Woodcock, I. Rietbrock, H. Voehringer and N. Rietbrock, veraparnil disposition in liver disease and intensivecase patients: kinetics, clearance, and apparent blood flow relationships. Clinical Pharmacology and Therapeutics. 29, 27-34 (1981) https://doi.org/10.1038/clpt.1981.5
  10. M. Eichelbaum, M. Albrecht, K Kliems, K Schafe and A Somogyi, Influence of mesocaval shunt surgery on verapamil kinetics, bioavailability and response. British Journal of Clinical Pharmacology, 10, 527-529 (1980) https://doi.org/10.1111/j.1365-2125.1980.tb01800.x
  11. J.B. Schwartz, D.R Abernethy, A.A Taylor and J.R Mitchel, An investigation of the cause of accumulation of veraparnil during regular dosing in patients. British J. Clinical Pharmacology, 19, 512-516 (1985) https://doi.org/10.1111/j.1365-2125.1985.tb02678.x
  12. S.B. Freedman, DR Richmond, J.J. AsWey and D.T. Kelly, veraparni1 kinetics in normal subjects and patients with coronary artery spasm. Clinical Pharmacology and Thera-peutics, 30, 644-652 (1981) https://doi.org/10.1038/clpt.1981.216
  13. M. Eichelbaum, P. Birkel, E. Grube, U. Gutgemann and A Somogyi, Effects of veraparnil on PR intervals in relation to veraparnil plasma levels following single i.v. and oral administration and during chronic treatment. Klinische Wochenschrift. 58, 919-925 (1980) https://doi.org/10.1007/BF01477049
  14. G. Mikus, Die Anwendung eines mit stabilen isotopen markierten Arzneimittels zur sirnultanen Bestimmung der relativen biologischem Verfugbarkeit einer verapamil retard Thesis, University of Bonn. (1985)
  15. J.A Dominic, D.w.A. Bourne, T.G. Tan, E.B. Kirsten and R.G. McAllister, The pharmacology of verapamil. III. Pharmaco-kinetics in normal subjects after intravenous drug admini-stration. J. Cardiovascular Pharmacology, 3, 25-38 (1981) https://doi.org/10.1097/00005344-198101000-00003
  16. R.G. McAllister, Clinical pharmacology of slow channel blocking agents. Progress in Cardiovascular Diseases, 25, 83102 (1982) https://doi.org/10.1016/0033-0620(82)90022-6
  17. F.X. McGowan, MJ. Reiter, ELe. Pritchett and D.G. Shand, veraparnil plasma binding: Relationship to alphajacid glycoprotein and drug efficacy. Clinical Pharmacology and Therapeutics, 33, 485-490 (1983) https://doi.org/10.1038/clpt.1983.66
  18. D.L. Keefe, YG. Yee and RE. Kates, veraparnil protein binding in patients and in normal subjects. Clin. Pharm. and Therapeutics, 29, 21-26 (1981) https://doi.org/10.1038/clpt.1981.4
  19. C.M. Loi, D.E. Rollins, G.E. Dukes and Peat, M. A Effect of cirnetidine on veraparnil disposition. Clin. Pharm. and Therapeutics, 37, 654-657 (1985) https://doi.org/10.1038/clpt.1985.106
  20. L.M. Johnson, S.M. Lankford and SA Bai, The influence of cirnetidine on the pharmacokinetics of the enantiomers of veraparnil in the dog during multiple oral dosing. J. Vet. Pharmacol. Ther., 18, 117-123 (1995) https://doi.org/10.1111/j.1365-2885.1995.tb00564.x
  21. L.M.H. Wing, J.O. Miners and K.I. Lillywhite, veraparnil disposition effects of sulphinpyrazone and cirnetidine. British Journal of Clinical Pharmacology, 19, 385-391 (1985) https://doi.org/10.1111/j.1365-2125.1985.tb02658.x
  22. D.R. Abernethy, lB. Schwatz and E.L. Todd, Lack of interaction between verapamil and cirnetidine. Clinical Pharmacology and Therapeutics, 38, 342-349 (1985) https://doi.org/10.1038/clpt.1985.183
  23. P.C. Ho, K. Ghose, D. Saville and S. Wanwirnolruk, Effect of grapefruit juice on the pharmacokinetics and pharmacody-namics of veraparnil enantiomers in healthy volunteers. Eur. J. Clin. Pharmacol, 56, 693-698 (2000) https://doi.org/10.1007/s002280000189
  24. U. Fuhr, H. Muller-Peltzer, R Kern and S. Harder, Effect of grapefruit juice and smoking on veraparnil concentration steady state. Eur. J. Clin. Pharmacol, 58, 45-53 (2002) https://doi.org/10.1007/s00228-002-0436-7
  25. R Zaidenstein, Y. Dishi, M. Gips, S. Soback, N. Cohen, J. Weissgarten, A Blatt and A Golik, The effect of grapefruit juice on the pharmacokinetics of orally administered veraparniI. Eur. J. Clin. Pharmacol, 54, 337-340 (1988) https://doi.org/10.1007/s002280050470
  26. E. Verzino, B. Kaplan, J.Y. AsWey and M. Burdette, verapamil aspirin interaction. Ann. Pharmacother, 28, 536-7 (1994)
  27. D. Orszulak-Michalak, AK Wiktorowska-Owczarek and J. Owczarek, Influence of midazolam on pharmacokinetics of veraparni1 in rabbits. Poz. 1. Pharmacol, 54, 501-506 (2002)
  28. R.A Lugo. and M.e. Nahata, veraparnil interaction with ceftriaxone and clindamycin. Ann. Pharmacother, 27, 877-80 (1993) https://doi.org/10.1177/106002809302700711
  29. R. Sandstrom, A Karlsson, L. Knutson and H. Lennernas, Jejunal absorption and metabolism of R/S-verapamil in humans. Pharm. Res., 15, 856-862 (l998) https://doi.org/10.1023/A:1011916329863
  30. Y.J. Wacher, C.Y. Wu and L.Z. Benet, Overlapping substrate specificities and tissue distribution of cytochrome p450 3A and P-glycoprotein: implications for drug delivery and activity in cancer chemotherapy. Mol. Carcinog., 13, 129-134 (1995) https://doi.org/10.1002/mc.2940130302
  31. V. Cody, Plant flavoniods in biology and medicine. Prog. Clin. BioI. Res., 213, 233-239 (1986)
  32. V. Cody, Plant flavonoids in biology and medicine, part . Prog Clin. BioI. Res., 280, 111-120 (1988)
  33. P.C.H. Hollman, M.V.D. Gaag and M.V.D. Mengelers, Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. Am. J. Clin. Nutr., 62, 1276-1282 (1995) https://doi.org/10.1093/ajcn/62.6.1276
  34. U. Takahama, Inhibition of lipoxygenase-dependent lipid peroxidation by quercetin: mechanism of antioxidative function. Phytochemistry, 24, 1443-1446 (1985) https://doi.org/10.1016/S0031-9422(00)81040-7
  35. E.N. Frankel, J.B. German, E. Parks and J.E. Kinsella, Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wind. The Lancet., 341, 454-457 (1993) https://doi.org/10.1016/0140-6736(93)90206-V
  36. M.T. Murray, Quercetin: Nature's antihistamine. Better Nutrition, 60, 10-16 (1998)
  37. W. Davis, M.S. Lamson, S. Matthew and N.D. Brignall, Antioxidants cancer : Quercetin. Alternative Medicine Review, 5, 196-208 (2000)
  38. D.R. Ferry, A. Smith, J. Malkhandi, DW. Fyfe, P.G. deTakats, D. Anderson, J. Baker and DR Kerr, Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clinical Cancer Research, 2, 659-668 (1996)
  39. J. Terao, M. Piskula, C. Rice-Evans and L. Packer, Flavonoids in health and disease, Marcel Dekker, New York: pp. 277-293 (1998)
  40. G. Soambia, EO. Ranellett, Panici, P.E. D.R. Vincenzo, G. Bonanno, G. Frrandina, M. Piantelli, S. Bussa, C. Rurni and M. Ciantriglia, Quercetin potentiates the effect of adriamycin in a multidrug-resistant MCF-7 human breast-cancer cell line: P-glycoprotein as a possible target. Cancer Chemother. Pharmacal, 36, 448-450 (1995)
  41. C.H. Choi, N. Romiti, E Cervelli and R. Tongiani, Effect of flavonols on P-glycoprotein activety in cultured rat hepatocytes. Life Sciences, 57, 1741-1750 (1995) https://doi.org/10.1016/0024-3205(95)02152-9
  42. H. Zhang, C.W Wong, P.G. Coville and S. Wanwimolruk, Effect of the grapefruit flavonoid naringen on pharmacokinetics of quinine in rats. Drug Metabol. Drug Interact, 17, 351-363 (2000)
  43. G.N. Kumar, UK Walle and T. Walle, Cytochrome P450 3Amediated human liver microsomal taxol to 6 alphahydroxylation. J. Pharmacal. Exp. Ther., 268, 1160-1165 (1994)
  44. A. Rahman, KR Korzekwa, J. Grogan, F.J. Gonzalez and J.W Harris, Selective biotransformation of taxol to 6 alphahydroxytaxo1 by human cytochrome P450 2C8. Cancer Res. 54, 5543-5546 (1994)
  45. 식품의약품안전청, 국립독성연구소, 생물학적동등성시험 펴시준지침, 식품의약품안전청, pp. 142-146 (2003)
  46. M.L. Rocci and W.j. Jusko, 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
  47. J.A. Endicott and V. Ling, The biochemistry of P-glycoprotein mediated multidrug resistance. Ann. Rev. Biochem., 58, 137-171 (1989) https://doi.org/10.1146/annurev.bi.58.070189.001033
  48. J.S. Choi, HK Choi and S.c. Shin, Enhanced paclitaxel bioavailability after oral administration of paclitaxel or prodrug to rats pretreated with quercetin. European Journal of Phannaceutics and Biopharmaceutics. in press (2004)
  49. S.L. Hsiu, Y.C. Hou, Y.H. Wang, C.W. Tsao, S.E Su and P.D. Chao, 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