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http://dx.doi.org/10.4333/KPS.2005.35.2.101

Effect of Naringin on the Pharmacokinetics of Nifedipine in Rabbits  

Na, Chong-Hak (College of Pharmacy, Chosun University)
Choi, Jun-Shik (College of Pharmacy, Chosun University)
Publication Information
Journal of Pharmaceutical Investigation / v.35, no.2, 2005 , pp. 101-106 More about this Journal
Abstract
The pharmacokinetics of oral nifedipine (5 mg/kg) was studied in rabbits given after or simultaneously with naringin (1.5, 7.5 and 15 mg/kg, respectively). The area under the plasma concentration-time curve (AUC) and the peak concentration $(C_{max})$ of nifedipine coadministered or pretreated with naringin were significantly increased (p < 0.05, coad.; p < 0.01, pret.) compared with the control group. The absolute bioavailability (AB%) of nifedipine was significantly (p < 0.05, coad.; p < 0.01, pret.) higher by 22.3 - 28.1 % compared to the control (17.9%). The relative bioavailability (RB%) of nifedipine was higher by 1.24 - 1.43 times (coad.) and 1.32 -1.57 times (pret.) than those of the control, showing that preatreatrnent of naringin was more effective than that of the coadministration of naringin. Naringin did not show significant effect on the Tmax and $t_{1/2}$ of nifedipine. It is suggested that naringin may alter pharmacokinetic paramiters of nifedipine by inhibition of P-glycoprotein efflux pump and its first-pass metabolism. The dosage of nifedipine should be adjusted when it is administered with naringin in a clinical situation.
Keywords
Nifedipine; Naringin; Pharmacokinetics; P-glycoprotein; First-pass metabolism;
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1 P.M. Chaudhary, and I.B. Robinson, Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells, Cell., 66, 85-94 (1991)   DOI   ScienceOn
2 J. Van Asperen, O. Van Tellingen, A. Sparreboom, A.H. Schinkel, P. Borst, W.J. Nooijen and J.H. Beijnen, Enhanced oral bilavailability of diltiazem in mice treated with the pglycoprotein blocker, Br. J. Cancer., 76, 1181-1183 (1997)   DOI   ScienceOn
3 K. Ito, H. Kusuhara and Y. Sugiyama, Effects of intestinal CYP3A4 and P-glycoprotein on oral drug absorption theoretical approach, Pharm. Res., 16, 225-231 (1999)   DOI   ScienceOn
4 K. Ito, H. Kusuhara and Y. Sugiyama, Effects of intestinal CYP 3A4 and P-glycoprotein on oral drug absorption-theoretical approach. Pharm. Res., 16, 225 (1999)   DOI   ScienceOn
5 J.L. Biedler and H. Riehm, Cellular resistance to actinomycin D in Chinese hamster cells in vitro: crossresistance, radioautographic, and cytogenetic studies, Cancer Res., 30, 1174-1184 (1970)
6 J.M. Ford, Modulators of multidrug resistance preclinical studies, Hematol. Oncol. Clin. N. Am., 9, 337-361 (1995)
7 J.P. Fruehauf and A. Manetta, Use of extreme drug resistance assay to evaluate mechanisms of resistance in ovarian cancer: Taxol resistance and MDRI expression, Contrib. Gynecol. Obstet., 19, 39-52 (1994)
8 T. Endo, O. Kimura and M. Sakata, Effects of P-glycoprotein inhibitors on cadmium accumulation in cultured renal epithelial cells, LLC-PK1, and OK, Toxicol. Appl. Pharmacol., 185, 166-171 (2002)   DOI   ScienceOn
9 N. Hokama, N. Hobara, M. Sakai, H. Kameya, S. Ohshiro and M. Sakanashi, Influence of nicardipine and nifedipine on plasma carvedilol disposition after oral administration in rats, J. Pharm. Pharmacol., 54, 821-825 (2002)   DOI   ScienceOn
10 R.J. Nijveldt, E. van Nood, D.E.C. van Hoorn, P.G. Boelens, K. van Norren and P.A.M. van Leeuwen, Flavonoids: A review of probable mechanisms of action and potential applications. Am. J. Clin. Nutr., 74, 418-425 (2001)
11 H. Doostdar, M.D. Burke and R.T. Mayer, Bioflavonoids: Selective substrates and inhibitors for cytochrome P450 CYP1A and CYP1B1. Toxicology., 144, 31-38 (2000)   DOI   ScienceOn
12 P.D. Henry, Comparative pharmacology of calcium antagonists: nifedipine, verapamil and diltiazem, Am. J. Cardiol., 46, 1047-1058 (1980)   DOI   ScienceOn
13 M.L. Rocci and W.J. Jusko, LAGRAN program for area and moments in Pharmacokinetic analysis. Computer Programs in Biomedicine., 16, 203-209 (1983)   DOI   ScienceOn
14 M. M. Gottesman and I. Pastan, Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu. Rev. Biochem., 62, 385 (1993)   DOI   ScienceOn
15 D.G. Walter, B.S. Gruchy, A.G. Renwick and C.F. George, The first pass metabolism of nifedipine in man, Br. J. Clin. Pharmacol., 18, 951-954 (1984)   DOI   ScienceOn
16 J.C. Kolars, P. Schmiedlin-Ren, W.O. Dobbins 3rd, J. Schuetz, S.A. Wrighton and P.B. Watkins, Heterogeneity of cytochrome P450IIIA expression in rat gut epithelia. Gastroenterology., 102, 1186-1198 (1992)
17 R.A. Dixon and C. Steele, Flavonoids and isoflavonoids-gold mine for metabolic engineering. Trends Plant Sci., 4, 394-400 (1999)   DOI   ScienceOn
18 J. Dupuy, G. Larrieu, J.F. Sutra, A. Lespine and M. Alvinerie, Enhancement of moxidectin bioavailability in lamb by a natural flavonoid: Quercetin. Vet. Parasitol., 112, 337-347 (2003)   DOI   ScienceOn
19 K.D. Raemsch and J.C. Sommer, Pharmacokinetics and metabolism of nifedipine, Hypertension., 5, 18-24 (1983)
20 E.M. Sorkin, S.P. Clissold and R.N. Brogden, Nifedipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in ischaemic heart disease, hypertension and related cardiovascular disorders, Drugs., 30, 182-274 (1985)   DOI   ScienceOn
21 C. Iribarne, L.G. Dreano, J.F. Bardou, G. Menez and F. Berthou, Interaction of methadone with substrates of human hepatic cytochrome P450 3A4, Toxicology., 117, 13-23 (1997)   DOI   ScienceOn
22 H.A. Bardelmeijer, J.H. Beijnen, K.R. Brouwer, H. Rosing, W.J. Nooijen, J.H. Schellens and O. van Tellingen, Increased oral bioavailability of paclitaxel by GF120918 in mice through selective modulation of P-glycoprotein. Clin. Cancer Res., 6, 4416-4421 (2000)
23 The Merck Index, 12th Edition, Merck and Company., Rahway, USA., 6512 (1996)
24 F.P. Guengerich, W.R. Brian and M. Iwasaki, et al., Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrome P-450 lIIA4, J. Med. Chem., 4, 1838-1844 (1991)
25 P.B. Watkins, S.A. Wrighton, E.G. Schuetz, D.T. Molowa and P.S. Guzelian, Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man, J. Clin. Invest., 80, 1029-1036 (1987)   DOI
26 M.M. Gottesman and I. Pastan, Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu. Rev. Biochem., 62, 385-427 (1993)   DOI   ScienceOn
27 L.-S.L. Gan, M.A. Moseley, B. Khosla, P.F. Augustijns, T.P. Bradshaw, R.W. Hendren and D.R. Thakker, 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)
28 P.B. Watkins, The barrier function of CYP3A4 and Pglycoprotein in the small bowel, Adv. Drug Deliv. Rev., 27, 161-170 (1996)   DOI   ScienceOn
29 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)   DOI
30 P. Hodek, P. Trefil and M. Stiborova, Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450. Chem. Biol. Interact., 139, 1-21 (2002)   DOI   ScienceOn
31 D.H. Kim, E.A. Jung, I.S. Sohng, 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)   DOI
32 H. Zhang, C.W. Wong, P.G. Coville and S. Wanwimolruk, Effect of the grapefruit flavonoid naringin on pharmacokinetics of quinine in rats. Drug Meta. Drug Interact., 17, 351-363 (2000)
33 P.C. Ho, D.J. Saville and S. Wanwimolruk, Inhibition of human CYP3A4 activity by grapefruit flavonoids, furanocoumarins and related compounds. J. Pharm. Pharm. Sci., 4, 217-227 (2001)
34 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)   DOI   ScienceOn
35 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)   DOI   ScienceOn
36 J.S. Choi and S.C. Shin, Enhanced paclitaxel bioavailability after oral coadministration of paclitaxel prodrug with naringin to rats. Int. J. Pharm., 23, 149-156 (2005)
37 J.S. Grundy, R. Kherani and R.T. Foster, Sensitive highperformance liquid chromatographic assay for nifedipine in human plasma utilizing ultraviolet detection, J. Chromatogr. B. Biomed. Appl., 654, 146-151 (1994)   DOI   ScienceOn