Browse > Article

Effect of Naringin Pretreatment on Bioavailability of Verapamil in Rabbits  

Yeum, Cheul-Ho (College of Medicine, Chosun University)
Choi, Jun-Shik (College of Pharmacy, Chosun University)
Publication Information
Archives of Pharmacal Research / v.29, no.1, 2006 , pp. 102-107 More about this Journal
Abstract
The aim of present study is to investigate the effect of naringin on the pharmacokinetics of verapamil and its major metabolite, norverapamil in rabbits. The pharmacokinetic parameters of verapamil and norverapamil were determined after administering verapamil (9 mg/kg) orally to rabbits in the pretreated with naringin (1.5, 7.5, and 15 mg/kg). Naringin pretreatment significantly altered the pharmacokinetic parameters of verapamil. Compared with the control group (given verapamil alone), the $K_a,\;C_{max}$ and AUC of verapamil were significantly (p<0.05 or p<0.01) increased in the pretreatment of naringin, However there were no significant change in $T_{max}\;and\;t_{1/2}$ of verapamil. Consequently, pretreatment of naringin significantly (p<0.05, p<0.01) increased the AB% of verapamil significantly in a dose dependent manner (p<0.05 or p<0.01 ), and elevated the RB% of verapamil by 1.26- to 1.69-fold. the MR of verapamil were significantly (p<0.05) increased in the pretreatment of naringin, implying that pretreatment of naringin may effectively inhibit the CYP3A4-mediated metabolism of verapamil. In conclusion, pretreatment of naringin enhanced the oral bioavailability of verapamil. Based on these results, the verapamil dosage should be adjusted when given with naringin or a naringin-containing dietary supplement.
Keywords
Naringin; Verapamil; CYP3A4; Pharmacokinetics; Rabbit;
Citations & Related Records

Times Cited By Web Of Science : 4  (Related Records In Web of Science)
Times Cited By SCOPUS : 4
연도 인용수 순위
1 Ader, P., Wessmann, A., and Wolffram, S., Bioavailability and metabolism of the flavonol quercetin in the pig. Free Radical Biol. Med., 28, 1056-1067 (2000)   DOI   ScienceOn
2 Bardelmeijer, H. A., Beijnen, J. H., Brouwer, K. R., Rosing, H., Nooijen, W. J., Schellens, J. H., and van Tellingen, O., Increased oral bioavailability of paclitaxel by GF120918 in mice through selective modulation of P-glycoprotein. Clin. Cancer Res., 6, 4416-4421 (2000)
3 Benet, L. Z., Cummins, C. L., and Wu, C. Y., Transporterenzyme interactions: implications for predicting drug-drug interactions from in vitro data. Curr. Drug Metab., 4, 393-398 (2003)   DOI   ScienceOn
4 Cummins, C. L., Jacobsen, W., and Benet, L. Z., Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP3A4. J. Pharmacol. Exp. Ther., 300, 1036-1045 (2002)   DOI   ScienceOn
5 Doppenschmitt, S., Spahn-Langguth, H., Regardh, C. G., and Langguth, P., Role of P-glycoprotein-mediated secretion in absorptive drug permeability: An approach using passive membrane permeability and affinity to P-glycoprotein. J. Pharm. Sci., 88, 1067-1072 (1999)   DOI
6 Eichelbaum, M., Mikus, G., and Vogelgesang, B., Pharmacokinetics of (+)-,(-)- and (${\pm}$)-verapamil after intravenous administration. Brit. J. Clin. Pharmacol., 17, 453-458 (1984)   DOI   ScienceOn
7 Gould, B. A., Mann, S., Kieso, H., Bala Subramanian, V., and Raftery, E. B., The 24-hour ambulatory blood pressure proflie with verapamil. Circulation, 65, 22-27 (1982)   DOI   ScienceOn
8 Kroemer, H. K., Gautier, J. C., Beaune, P., Henderson, C., Wolf, C. R., and Eichelbaum, M., Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn- Schmiedeberg's Arch. Pharmacol., 348, 332-337 (1993)
9 Manach, C., Morand, C., Demigne, C., Texier, O., Regerat, F., and Remesy, C., Bioavailability of rutin and quercetin in rats. FEBS Lett., 409, 12-16 (1997)   DOI   ScienceOn
10 Rahman, A., Korzekwa, K. R., Grogan, J., Gonzalezs, F. J., Harris, J. W., Selective biotransformation of taxol to 6$\alpha$- hydroxytaxol by human cytochrome P450 2C8. Cancer Res., 54, 5543-5546 (1994)
11 Schomerus, M., Spiegelhaider, B., Stieren, B., and Eichelbaum, M., Physiologic disposition of verapamil in man. Cardiovasc. Res., 10, 605-612 (1976)   DOI   ScienceOn
12 Takanaga, H. A., Ohnishi, H., and Matsuo, 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)   DOI
13 Eagling, V. A., Profit, L., and Back, D. J., 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)   DOI   ScienceOn
14 Buse, D., Cosme, J. P., Beaune, H. K., and Kroemer, M., Eichelbaum, Cytochromes of the P450 2C subfamily are the major enzymes imvolved in the O-demethylation of verapamil in humans. Naunyn-Schmiedeberg's Arch. Pharmacol., 353, 116-121 (1995)
15 Dey, C. S., Varma, M. V., Ashokraj, Y., and Panchagnula, R., Pglycoprotein inhibitors and their screening: a perspective from bioavailability enhancement. Pharmacol. Res., 48, 347- 359 (2003)   DOI   ScienceOn
16 Eichelbaum, M., Remberg, E. G., Schomerus, M., and Dengler, H. J., The metabolism of D,L(14C) verapamil in man. Drug Metab. Dispos., 7, 145-148 (1979)
17 Dixon, R. A. and Steele, C., Flavonoids and isoflavonoids-gold mine for metabolic engineering. Trends Plant Sci., 4, 394-400 (1999)   DOI   ScienceOn
18 Meng, X., Maliakal, P., Lu, H., Lee, M. J., and Yang, C. S., Urinary and plasma levels of resveratrol and quercetin in humans, mice, and rats after ingestion of pure compounds and grape juice. J. Agric. Food Chem., 52, 935-942 (2004)   DOI   ScienceOn
19 Krecic-Shepard, M. E., Barmas, C. R., and Schwartz, J. B., Faster clearance of sustained release verapamil in men versus women: Continnuing observations on sex specific differences after oral administration of verapamil. Clin. Pharmacol. Ther., 68, 286-292 (2000)   DOI   ScienceOn
20 Nijveldt, R. J., van Nood, E., van Hoorn, D. E. C., Boelens, P. G.,van Norren, K., and van Leeuwen, P. A. M., Flavonoids: a review of probable mechanisms of action and potential applications. Am. J. Clin. Nutr., 74, 418-425 (2001)   DOI
21 Giacomini, J. C., Nelson, W. L., Theodore, L., Wong, F. M., Rood, D., and Giacomini, M., The pharmacokinetics and pharmacodynamics of d- and dl-verapamil in rabbits. J. Cardiovasc Pharmacol., 7, 469-475 (1985)   DOI
22 Lewis, G. R., Morley, K. D., Lewis, B. M., and Bones, P. J., The treatment of hypertension with verapamil. NZ Medical J., 87, 351-354 (1978)
23 Takahama, U., Inhibition of lipoxygenase-dependent lipid peroxidation by quercetin: mechanism of antioxidative function. Phytochemistry, 24, 1443 -1446 (1985)   DOI   ScienceOn
24 Kumar, G. N., Walle, U. K., and Walle, T., Cytochome P450 3Amediated human liver microsomal taxol 6$\-hydroxylation. J. Pharmacol. Exp. Ther., 268, 1160-1165 (1994)
25 Zhang, H., Wong, C. W., Coville, P. G., and Wanwimolruk, S., Effect of the grapefruit flavonoid naringin on pharmacokinetics of quinine in rats. Drug Metabol. Drug Interact., 17, 351-363 (2000)
26 Mori, Y., Hanada, K., Mori, T., Tsukahara, Y., Hashiguchi, M., and Ogata, H., Stereoselective pharmacokinetics and pharmacodynamics of verapamil and norverapamil in rabbits. Biol. Pharm. Bull., 24, 806-810 (2001)   DOI   ScienceOn
27 Cody, V., Plant Flavonoids in Biology and Medicine, part II. Prog. Clin. Biol. Res., 280, 111-120 (1988)
28 Rocci, M. L. and Jusko, W. J., LAGRAN program for area and moments in pharmacokinetic analysis. Comp. Prog. In. Biomed., 16, 203-209 (1983)   DOI   ScienceOn
29 Cody, V., Plant Flavoniods in Biology and Medicine. Prog. Clin. Biol. Res., 213, 233-239 (1986)
30 Dupuy, J., Larrieu, G., Sutra, J. F., Lespine, A., and Alvinerie, M., Enhancement of moxidectin bioavailability in lamb by a natural flavonoid. Vet. Parasitol., 112, 337-347 (2003)   DOI   ScienceOn
31 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)   DOI   ScienceOn
32 Fleckenstein, A., Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Ann. Rev. Pharmacol. Toxicol., 17, 149-166 (1977)   DOI   ScienceOn
33 Kim, H. J. and Choi, J. S., Effects of naringin on the pharmacokinetics of verapamil and one of its metabolites, narverapamil, in rabbits. Biopharm. Drug Dispos., 26, 295- 300 (2005)   DOI   ScienceOn
34 Wacher, V. J., Salphati, L., and Benet, L. Z., Active secretion and enterocytic drug metabolism barriers to drug absorption. Adv. Drug Deliver. Rev., 20, 99-112 (1996)   DOI   ScienceOn
35 Davis, J., Williams, L. S., Hill, D., and Lowenthal, D. T., Effects of fosinopril or sustained-release verapamil on blood pressure and serum techolamine concentrations in elderly hypertensive men. Am. J. Ther., 7, 3-9 (2000)   DOI
36 Doostdar, H., Burke, M. D., and Mayer, R. T., Bioflavoniods: selective substrates and inhibitors for cytochrome P450 CYP1A and CYP1B1. Toxicology, 144, 31-38 (2000)   DOI   ScienceOn
37 Kim, D. H., Jung, E. A., Shong, I. S., and Han, J. A., Intestinal bacterial metabolism of flavonoids and its relation to some biological activities. Arch. Pharm. Res., 21, 17-23 (1998)   DOI
38 Ho, P. C., Saville, D. J., and Wanwimolruk, S., Inhibition of human CYP3A4 activity by grapefruit flavonoids, furanocoumarins and related compounds. J. Pharm. Pharm. Sci., 4, 217-227 (2001)