토끼에서 나린진이 니모디핀의 생체이용률에 미치는 영향
Effects of Naringin on the Bioavailability of Nimodipine in Rabbits
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
The purpose of this study was to investigate the effect of naringin, one of flavonoids, on the pharmacokinetics and bioavailability of nimodipine in rabbits. Pharmacokinetic parameters of nimodipine were determined in rabbits after oral administration of nimodipine (16 mg/kg) with or without naringin (1, 5 or 15 mg/kg). Nimodipine was analyzed by high performance liquid chromatography using Hypersil ODS column. Naringin significantly (p<0.05) increased the area under the plasma concentration-time curve (AUC) and the peak concentration (Cmax) of nimodipine at 5 and 15 mg/kg. The absolute bioavailability (AB%) of nimodipine by prescence of naringin (5 or 15 mg/kg) increased from 32.2-36.9% (p<0.05) compared to the control (22.0%). However, presence of naringin had no significant effect on the elimination rate constant (Kel) of nimodipine. There were no apparent changes of the time of peak concentration (Tmax) of nimodipine by coadministration. These results suggest that the increased bioavailability and the significant changes of these pharmacokinetic parameters of nimodipine by naringin may be attributed to the potential of narigin to inhibit cytochrome P450 (CYP) 3A4 and P-glycoprotein efflux pump in the liver and intestinal mucosa.
Abstract
The purpose of this study was to investigate the effect of naringin, one of flavonoids, on the pharmacokinetics and bioavailability of nimodipine in rabbits. Pharmacokinetic parameters of nimodipine were determined in rabbits after oral administration of nimodipine (16 mg/kg) with or without naringin (1, 5 or 15 mg/kg). Nimodipine was analyzed by high performance liquid chromatography using Hypersil ODS column. Naringin significantly (p<0.05) increased the area under the plasma concentration-time curve (AUC) and the peak concentration (Cmax) of nimodipine at 5 and 15 mg/kg. The absolute bioavailability (AB%) of nimodipine by prescence of naringin (5 or 15 mg/kg) increased from 32.2-36.9% (p<0.05) compared to the control (22.0%). However, presence of naringin had no significant effect on the elimination rate constant (Kel) of nimodipine. There were no apparent changes of the time of peak concentration (Tmax) of nimodipine by coadministration. These results suggest that the increased bioavailability and the significant changes of these pharmacokinetic parameters of nimodipine by naringin may be attributed to the potential of narigin to inhibit cytochrome P450 (CYP) 3A4 and P-glycoprotein efflux pump in the liver and intestinal mucosa.
참고문헌 (22)
- Scholz H, "Pharmacological aspects of calcium channel blockers. Cardiovasc", Drugs Ther, 10, pp.869~872 (1997)
- Epstein M, "Loutzenhister RD. Effects of calcium antagonists on renal hemodynamics", Am J. Kidney Dis, 16, pp.10~14 (1990)
- Kazda S, "Cerebrovascular effects of the calcium antagonistic dihydropyridine derivative nimodipine in animal experiments", Arzneimittelforschung, 32, pp.331~338 (1982)
- nimodipine in rat, dog and monkey, "Arzneimittelforschung", 1985, 1781~1786
- nimodipine in rat, dog and monkey, "Arzneimittelforschung", 1985, 1787~1794
- Ramsch KD, "Overview on pharmacokinetics of nimodipine in healthy volunteer and in patients with subarachnoid hemorrhage", Neurochirurgia, 28, pp.74~78 (1985)
- Scherling D, "Biotransformation of nimodipine in rat, dog and monkey", Arzneimittelforschung, 41, pp.392~398 (1991)
- Guengerich FP, "Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrom P-450IIIA4", J Med Chem, 34, pp.1834~1844 (1991)
- Fuhr U, "Grapefruit juice increases oral nimodipine bioavailability", Int J Clin Pharmacol Ther, 36, pp.126~132 (1998)
- Zhang L, "P-glycoprotein restricted transport of nimodipine across blood-brain barrier", Acta Pharmacol Sin, 24, pp.903~906 (2003)
- Hodek P, "Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450", Chem Biol Interact, 139, pp.1~21 (2002)
- Dupuy J, "Enhancement of moxidectin bioavailability in lamb by a natural flavonoid: Quercetin", Vet Parasitol, 112, pp.337~347 (2003)
- Bardelmeijer HA, "Increased oral bioavailability of paclitaxel by GF120918 in mice through selective modulation of P-glycoprotein", Clin Cancer Res, 6, pp.4416~4421 (2000)
- "The Merck Index, 12th Edition", pp.6512~ (1996), Merck and Company
- Kim DH, "Intestinal bacterial metabolism of flavonoids and its relation to some biological activities", Arch Pharm Res, 21, pp.17~23 (1998)
- Zhang H, "Effect of the grapefruit flavonoid naringin on pharmacokinetics of quinine in rats", Drug Meta Drug Interact, 17, pp.351~363 (2000)
- Ho PC, "Inhibition of human CYP3A4 activity by grapefruit flavonoids, furanocoumarins and related compounds", J Pharm Pharm Sci, 4, pp.217~227 (2001)
- Takanaga H, "Inhibition of vinblastine efflux mediated by P-glycoprotein by grapefruit juice components in caco-2 cells", Biol Pharm Bull, 21, pp.1062~1066 (1998)
- Eagling VA, "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, pp.543~552 (1999)
- Qian M, "High-perfomance liquid chromatographic determinination of the calcium channel blocker nimodipine in monkey plasma", J Chromatogr, 578, pp.316~320 (1992)
- Choi JS, "Enhanced nimodipine bioavailability after oral administration of nimodipine with morin, a flavonoid, in rabbits", Arch Pharm Res, 29, pp.333~338 (2006)
- Choi JS, "Enhanced paclitaxel bioavailability after oral coadministration of paclitaxel prodrug with naringin to rats", Int J Pharm, 23, pp.149~156 (2005)