Abstract
The present study investigated the effect of fenugreek seed powder on disposition of CYP3A substrates, cyclosporine and carbamazepine. Rabbits were treated with fenugreek seed powder (300 mg/kg p.o.) for 8 days and on 8th day the single dose of cyclosporine (30 mg/kg, p.o.) and carbamazepine (40 mg/kg, p.o.) were administered to the corresponding group after 1 h of fenugreek administration. Blood samples were drawn at several time points and analyzed by using UPLC-MS (cyclosporine) and HPLC (carbamazepine). Pharmacokinetic parameters were calculated by using PKSolver. The present investigation reveals that there was no statistically significant difference between pre- and post-treated pharmacokinetic parameters such as AUC0–t , AUC0–∞, C max, T max, T 1/2, K el, MRT0–∞, V z/F , and Cl/F for cyclosporine and carbamazepine. Two tailed “P” values for all these pharmacokinetic parameters were more than 0.05, indicating insignificant impact of fenugreek treatment on the disposition of cyclosporine and carbamazepine. Further, fenugreek may also not have any significant effect on the functionality of P-glycoprotein as cyclosporine is a substrate to P-glycoprotein. The outcomes of present study suggested that fenugreek may not likely to interfere cyclosporine and carbamazepine pharmacokinetics, when co-administered with these drugs.
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Al-Jasass FM, Al-Jasser MS (2012) Chemical composition and fatty acid content of some spices and herbs under Saudi Arabia conditions. Scientific World J 5 (Article ID 859892)
Azaizeh H, Saad B, Cooper E, Said O (2010) Traditional arabic and islamic medicine, a re-emerging health aid. Evid Based Complement Alternat Med (7)4:419–424
Barone GW, Gurley BJ, Ketel BL, Lightfoot ML, Abul-Ezz SR (2000) Drug interaction between St John’s wort and cyclosporine-A. Ann Pharmacother 34(9):1013–1016
Barone GW, Gurley BJ, Ketel BL, Abul-Ezz SR (2001) Herbal supplements: a potential for drug interactions in transplant recipients. Transplantation 71(2):239–241
Burstein AH, Horton RL, Dunn T, Alfaro RM, Piscitelli SC, Theodore W (2000) Lack of effect of St John’s Wort on carbamazepine pharmacokinetics in healthy volunteers. Clin Pharmacol Ther 68(6):605–612
Chen LC, Chen YF, Chou MH, Lin MF, Yang LL, Yen KY (2002) Pharmacokinetic interactions between carbamazepine and the traditional Chinese medicine Paeoniae Radix. Biol Pharm Bull 25(4):532–535
Chiang HM, Chao PD, Hsiu SL, Wen KC, Tsai SY, Hou YC (2006) Ginger significantly decreased the oral bioavailability of cyclosporine-A in rats. Am J Chin Med 34(5):845–855
Crettol S, Venetz JP, Fontana M, Aubert JD, Pascual M, Eap CB (2008) CYP3A7, CYP3A5, CYP3A4, and ABCB1 genetic polymorphisms, cyclosporine-A concentration, and dose requirement in transplant recipients. Ther Drug Monit 30(6):689–699
Dresser GK, Spence JD, Bailey DG (2000) Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet 38:41–57
Duclos J, Goecke H (2001) Hierba del clavo (Geumchiloense) modifying cyclosporine-A levels: potential risk for transplanted people. Rev Med Chill 129(7):789–790
Fahr A (1993) Cyclosporin clinical pharmacokinetics. Clin Pharmacokinet 24(6):472–495
Garg SK, Islam AS, Kumar N (1998) Effect of Septilin—a herbal preparation on pharmacokinetics of carbamazepine in rabbits. Indian J Physiol Pharmacol 42(4):527–532
Giessmann T, May K, Modess C, Wegner D, Hecker U, Zschiesche M, Dazert P, Grube M, Schroeder E, Warzok R, Cascorbi I, Kroemer HK, Siegmund W (2004) Carbamazepine regulates intestinal P-glycoprotein and multidrug resistance protein MRP2 and influences disposition of talinolol in humans. Clin Pharmacol Ther 76(3):192–200
Hassanzadeh E, Chaichi MR, Mazaheri D, Rezazadeh S, Badi HAN (2011) Physical and chemical variabilities among domestic iranian Trigonella foenum-graecum (Trigonella foenum-graceum) seeds. Asian J Plant Sci 10:323–330
Hoareau L, DaSilva EJ (1999) Medicinal plants: a re-emerging health aid. EJB 2(2):56–70
Hu Z, Yang X, Chan SY, Heng PW, Chan E, Duan W, Koh HL, Zhou S (2005) Herb–drug interactions: a literature review. Drugs 65(9):1239–1282
Izzo AA (2005) Herb–drug interactions: an overview of the clinical evidence. FundamClinPharmacol 19(1):1–16
Kerr BM, Thummel KE, Wurden CJ, Klein SM, Kroetz DL, Gonzalez FJ, Levy RH (1994) Human liver carbamazepine metabolism. Role of CYP3A4 and CYP2C8 in 10,11-epoxide formation. Biochem Pharmacol 47(11):1967–1979
Lambert JP, Cormier J (2001) Potential interaction between warfarin and boldo-Trigonella foenum-graecum. Pharmacotherapy 21(4):509–512
Lee SY, Lee JY, Kang W, Kwon KI, Park SK, Oh SJ, Ma JY, Kim SK (2013a) Cytochrome P450-mediated herb–drug interaction potential of Galgeun-tang. Food Chem Toxicol 51:343–349
Lee SY, Lee JY, Kang W, Kwon KI, Oh SJ, Ma JY, Kim SK (2013b) In vitro and in vivo assessment of cytochrome P450-mediated herb–drug interaction of Ssang-hwa-tang. Food Chem 136(2):450–457
Madar Z, Abel R, Samish S, Arad J (1988) Glucose-lowering effect of Trigonella foenum-graecum in non-insulin dependent diabetics. Eur J Clin Nutr 42(1):51–54
Moore LB, Goodwin B, Jones SA, Wisely GB, Serabjit-Singh CJ, Willson TM, Collins JL, Kliewer SA (2000) St. John’s wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci USA 97(13):7500–7502
Moschella C, Jaber BL (2001) Interaction between cyclosporine-A and Hypericum perforatum (St. John’s wort) after organ transplantation. Am J Kidney Dis 38(5):1105–1107
Ohnishi N, Yonekawa Y, Nakasako S, Yokoyama T, Yoshioka M, Kuroda K (1999) Studies on interactions between traditional herbal and Western medicines. I. Effects of Sho-seiryu-to on the pharmacokinetics of carbamazepine in rats. Biol Pharm Bull 22(5):527–531
Ohnishi N, Nakasako S, Okada K, Umehara S, Takara K, Nagasawa K, Yoshioka M, Kuroda K, Yokoyama T (2001) Studies on interactions between traditional herbal and Western medicines. IV: lack of pharmacokinetic interactions between Saiko-ka-ryukotsu-borei-to and carbamazepine in rats. Eur J Drug Metab Pharmacokinet 26(1–2):129–135
Omeish AF, Abbadi W, Ghanma IM, Drabaa Z, Botoosh FA, Seif A, Massadeh M (2011) Hospital-based study on the use of herbal medicine in patients with coronary artery disease in Jordan. J Pak Med Assoc 61(7):683–687
Owen A, Pirmohamed M, Morgan P, Chadwick D, Park BK (2001) Carbamazepine is not a substrate for P-glycoprotein. Br J Clin Pharmacol 51(4):345–349
Qiu W, Jiang XH, Liu CX, Ju Y, Jin JX (2009) Effect of berberine on the pharmacokinetics of substrates of CYP3A and P-gp. Phytother Res 23(11):1553–1558
Saad B, Azaizeh H, Said O (2005) Tradition and perspectives of arab herbal medicine: a review. Evid Based Complement Alternat Med 2:475–479
Sharma RD (1986) Effect of Trigonella foenum-graecum seeds and leaves on blood glucose and serum insulin responses in human subjects. Nutr Res 6(12):1353–1364
Sharma RD, Sarkar A, Hazra DK, Misra B, Singh JB, Maheshwari SK, Sharma SK (1996) Hypolipidaemic Effect of Trigonella foenum-graecum seeds: a chronic study in non-insulin dependent diabetic patients. Phytother Res 10(4):332–334
Sowmya P, Rajyalakshmi P (1999) Hypocholesterolemic effect of germinated Trigonella foenum-graecum seeds in human subjects. Plant Foods Hum Nutr 53(4):359–365
Tang J, Song X, Zhu M, Zhang J (2009) Study on the pharmacokinetics drug–drug interaction potential of Glycyrrhiza uralensis, a traditional Chinese medicine, with lidocaine in rats. Phytother Res 23(5):603–607
Zhou SF (2008) Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Curr Drug Metab 9(4):310–322
Zhou J, Chan L, Zhou S (2012) Trigonelline: a plant alkaloid with therapeutic potential for diabetes and central nervous system disease. Curr Med Chem 19(21):3523–3531
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This work is supported by the National Plan for Science and Technology (NPST), King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia, under the project no. BIO1046-02-10.
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Al-Jenoobi, F.I., Alam, M.A., Alkharfy, K.M. et al. Pharmacokinetic interaction studies of fenugreek with CYP3A substrates cyclosporine and carbamazepine. Eur J Drug Metab Pharmacokinet 39, 147–153 (2014). https://doi.org/10.1007/s13318-013-0149-6
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DOI: https://doi.org/10.1007/s13318-013-0149-6