Pharmacokinetic drug interactions involving Ginkgo biloba

Drug Metabolism Reviews

Volumn 45, Issue 3, 2013, Pages 353-385

  Unger, Matthias ^a  

^a UNIVERSITY OF WÜRZBURG   (Germany)

Author keywords

Bioavailability; Cytochrome P450 enzymes; EGb 761; Flavonol glycosides; Ginkgo biloba; Ginkgolic acids; Herbal extracts; Organic anion transporting polypeptides; P glycoprotein; Terpene lactones

Indexed keywords

(3 NONADEC 8 ENYLBENZENE 1,2 DIOL); [4,4' (1,4 PENTADIENE 1,5 DIYL)DIPHENOL]; ACACETIN; AMENTOFLAVONE; APIGENIN; ATORVASTATIN; CALCEIN; COUMARIN DERIVATIVE; CYTOCHROME P450; DAUNORUBICIN; DIGOXIN; ETHOXYRESORUFIN; FEXOFENADINE; FLAVONE DERIVATIVE; FLAVONOID GLYCOSIDE; GINKGO BILOBA EXTRACT; GINKGOLIDE A; GINKGOLIDE B; GINKGOLIDE C; GINKGOLIDE J; ISORHAMNETIN; KAEMPFEROL; MYCOPHENOLIC ACID; MYRICETIN; QUERCETIN; SESAMIN; TAMARIXETIN; TERPENOID; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROIC ACID;

ALZHEIMER DISEASE; DRUG BLOOD LEVEL; DRUG DOSAGE FORM COMPARISON; DRUG INTERACTION; DRUG MEGADOSE; DRUG QUALITY; ENZYME INDUCTION; ENZYME INHIBITION; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LABORATORY; NONHUMAN; PHARMACOKINETICS; RECOMMENDED DRUG DOSE; REPEATED DRUG DOSE; REVIEW; SINGLE DRUG DOSE; TRANSCRIPTION INITIATION;

ANIMALS; DIETARY SUPPLEMENTS; GINKGO BILOBA; HERB-DRUG INTERACTIONS; HUMANS; PHYTOTHERAPY; PLANT EXTRACTS;

EID: 84880533608     PISSN: 03602532     EISSN: 10979883     Source Type: Journal    
DOI: 10.3109/03602532.2013.815200     Document Type: Review

References (191)

1. Abourashed EA, Khan IA. (2001). High-performance liquid chromatography determination of hydrastine and berberine in dietary supplements containing goldenseal. J Pharm Sci 90:817-822.
2. Almond LM, Hoggard PG, Edirisinghe D, et al. (2005). Intracellular and plasma pharmacokinetics of efavirenz in HIV-infected individuals. J Antimicrob Chemother 56:738-744.
3. Argikar UA, Remmel RP. (2009). Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDPglucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos 37:229-236.
4. Bailey DG, Dresser GK, Leake BF, Kim RB. (2007). Naringin is a major and selective clinical inhibitor of organic anion-transporting polypeptide 1A2 (OATP1A2) in grapefruit juice. Clin Pharmacol Ther 81: 495-502.
5. Baron-Ruppert G, Luepke NP. (2001). Evidence for toxic effects of alkylphenols from Ginkgo biloba in the hen's egg test (HET). Phytomedicine 8:133-138.
6. Bedir E, Tatli II, Khan RA, et al. (2002). Biologically active secondary metabolites from Ginkgo biloba. J Agric Food Chem 50:3150-3155.
7. Benet LZ. (2009). The drug transporter-metabolism alliance: Uncovering and defining the interplay. Mol Pharm 6:1631-1643.
8. Benet LZ, Izumi T, Zhang Y, et al. (1999). Intestinal MDR transport proteins and P-450 enzymes as barriers to oral drug delivery. J Control Release 62:25-31.
9. Biber A. (2003). Pharmacokinetics of Ginkgo biloba extracts. Pharmacopsychiatry 36:S32-S37.
10. Biber A, Koch E. (1999). Bioavailability of ginkgolides and bilobalide from extracts of Ginkgo biloba using GC/MS. Planta Med 65: 192-193.
11. Blumenthal M, Busse WR, Goldberg A, et al. (1998). The complete German Commission E monographs: Therapeutic guide to herbal medicines. Austin, TX: American Botanical Council; Boston (MA).
12. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. (2000). An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 7: 273-282.
13. Butterweck V, Derendorf H, Gaus W, et al. (2004). Pharmacokinetic herb-drug interactions: Are preventive screenings necessary and appropriate?. Planta Med 70:784-791.
14. Chang TK, Chen J, Teng XW. (2006). Distinct role of bilobalide and ginkgolide A in the modulation of rat CYP2B1 and CYP3A23 gene expression by Ginkgo biloba extract in cultured hepatocytes. Drug Metab Dispos 34:234-242.
15. Chang TK, Gonzalez FJ, Waxman DJ. (1994). Evaluation of triacetyloleandomycin, alpha-naphthoflavone and diethyldithiocarbamate as selective chemical probes for inhibition of human cytochromes P450. Arch Biochem Biophys 311:437-442.
16. Chatterjee SS, Doelman CJ, Noldner M, et al. (2005). Influence of the Ginkgo extract EGb 761 on rat liver cytochrome P450 and steroid metabolism and excretion in rats and man. J Pharm Pharmacol 57: 641-650.
17. Chauhan B, Yu C, Krantis A, et al. (2007). In vitro activity of uva-ursi against cytochrome P450 isoenzymes and P-glycoprotein. Can J Physiol Pharmacol 85:1099-1107.
18. Chen YC, Gotzkowsky SK, Nafziger AN, et al. (2006). Poor correlation between 6beta-hydroxycortisol: Cortisol molar ratios and midazolam clearance as measure of hepatic CYP3A activity. Br J Clin Pharmacol 62:187-195.
19. Cooper CL, van Heeswijk RP, Gallicano K, Cameron DW. (2003). A review of low-dose ritonavir in protease inhibitor combination therapy. Clin Infect Dis 36:1585-1592.
20. Cvetkovic M, Leake B, Fromm MF, et al. (1999). OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos 27:866-871.
21. DAB 2003. (2003). Monographie Eingestellter Ginkgotrockenextrakt, Deutsches Arzneibuch 2003. Stuttgart, Deutscher Apotheker-Verlag.
22. DeKosky ST, Williamson JD, Fitzpatrick AL, et al. (2008). Ginkgo biloba for prevention of dementia: A randomized controlled trial. JAMA 300:2253-2262.
23. Deng Y, Bi HC, Zhao LZ, et al. (2008a). Induction of cytochrome P450s by terpene trilactones and flavonoids of the Ginkgo biloba extract EGb 761 in rats. Xenobiotica 38:465-481.
24. Deng Y, Bi HC, Zhao LZ, et al. (2008b). Induction of cytochrome P450 3A by the Ginkgo biloba extract and bilobalides in human and rat primary hepatocytes. Drug Metab Lett 2:60-66.
25. Dirson G, Fernandez C, Hindlet P, et al. (2006). Efavirenz does not interact with the ABCB1 transporter at the blood-brain barrier. Pharm Res 23:1525-1532.
26. Drago F, Floriddia ML, Cro M, Giuffrida S. (2002). Pharmacokinetics and bioavailability of a Ginkgo biloba extract. J Ocul Pharmacol Ther 18:197-202.
27. Dresser GK, Kim RB, Bailey DG. (2005). Effect of grapefruit juice volume on the reduction of fexofenadine bioavailability: Possible role of organic anion transporting polypeptides. Clin Pharmacol Ther 77: 170-177.
28. Eichelbaum M, Reetz KP, Schmidt EK, Zekorn C. (1986). The genetic polymorphism of sparteine metabolism. Xenobiotica 16: 465-481.
29. EMA. (2010). Guideline on the investigation of bioequivalence. Committee for human medicinal products, European Medicines Agency, London.
30. EMA. (2012). Guideline on the investigation of drug interactions. Committee for human medicinal products, European Medicines Agency, London.
31. Engelsen J, Nielsen JD, Winther K. (2002). Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin treated outpatients. A randomised, double blind, placebo-crossover trial. Thromb Haemost 87:1075-1076.
32. ESCOP. (2003). Ginkgo Folium, Ginkgo Leaf. In: ESCOP ed. ESCOP Monographs, 2nd edition. Stuttgart, New York: Thieme, 178-210.
33. Etheridge AS, Black SR, Patel PR, et al. (2007). An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constituents. Planta Med 73:731-741.
34. Fan L, Mao XQ, Tao GY, et al. (2009a). Effect of Schisandra chinensis extract and Ginkgo biloba extract on the pharmacokinetics of talinolol in healthy volunteers. Xenobiotica 39: 249-254.
35. Fan L, Tao GY, Wang G, et al. (2009b). Effects of Ginkgo biloba extract ingestion on the pharmacokinetics of talinolol in healthy Chinese volunteers. Ann Pharmacother 43:944-949.
36. Flexner C. (2000). Dual protease inhibitor therapy in HIV-infected patients: Pharmacologic rationale and clinical benefits. Annu Rev Pharmacol Toxicol 40:649-674.
37. Fourtillan JB, Brisson AM, Girault J, et al. (1995). Proprietes pharmacocinetiques du bilobalide et des ginkgolides A et B chez le sujet sain pres administrations intraveineuses et orales d'extrait de Ginkgo biloba (EGb 761). Therapie 50:137-144.
38. Frank A, Unger M. (2006). Analysis of frankincense from various Boswellia species with inhibitory activity on human drug metabolising cytochrome P450 enzymes using liquid chromatography mass spectrometry after automated on-line extraction. J Chromatogr A 1112:255-262.
39. Fuchikami H, Satoh H, Tsujimoto M, et al. (2006). Effects of herbal extracts on the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos 34:577-582.
40. Galluzzi S, Zanetti O, Binetti G, et al. (2000). Coma in a patient with Alzheimer's disease taking low dose trazodone and gingko biloba. J Neurol Neurosurg Psychiatry 68:679-680.
41. Galteau MM, Shamsa F. (2003). Urinary 6beta-hydroxycortisol: A validated test for evaluating drug induction or drug inhibition mediated through CYP3A in humans and in animals. Eur J Clin Pharmacol 59:713-733.
42. Gaudineau C, Beckerman R, Welbourn S, Auclair K. (2004). Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract. Biochem Biophys Res Commun 318: 1072-1078.
43. German Commission E. (1994). Monograph on dry extracts (35-67:1) made of G. biloba leaves. Bundesanzeiger Nr 133. Koln, Germany, Bundesanzeiger Verlagsgesellschaft
44. Glisson JK, Minor DS, Walker LA, Gurley BJ. (2011). Dietary supplements: Safety issues and quality control. Arch Intern Med 171:476-477.
45. Greenblatt DJ, von Moltke LL, Luo Y, et al. (2006). Ginkgo biloba does not alter clearance of flurbiprofen, a cytochrome P450-2C9 substrate. J Clin Pharmacol 46:214-221.
46. Gurley BJ, Gardner SF, Hubbard MA, et al. (2002). Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 72:276-287.
47. Gurley BJ, Gardner SF, Hubbard MA, et al. (2005a). Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John's wort, garlic oil Panax ginseng and Ginkgo biloba. Drugs Aging 22:525-539.
48. Gurley BJ, Gardner SF, Hubbard MA, et al. (2005b). In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 77:415-426.
49. Gurley BJ, Swain A, Hubbard MA, et al. (2008a). Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo. Clin Pharmacol Ther 83:61-69.
50. Gurley BJ, Swain A, Hubbard MA, et al. (2008b). Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: Effects of milk thistle, black cohosh, goldenseal, kava kava St. John's wort, and Echinacea. Mol Nutr Food Res 52:755-763.
51. Hamik A, Peroutka SJ. (1989). 1-(m-chlorophenyl)piperazine (mCPP) interactions with neurotransmitter receptors in the human brain. Biol Psychiatry 25:569-575.
52. Hanrahan JR, Chebib M, Johnston GA. (2011). Flavonoid modulation of GABA(A) receptors. Br J Pharmacol 163:234-245.
53. Hariparsad N, Chu X, Yabut J, et al. (2009). Identification of pregnane-X receptor target genes and coactivator and corepressor binding to promoter elements in human hepatocytes. Nucleic Acids Res 37: 1160-1173.
54. Hecker H, Johannisson R, Koch E, Siegers CP. (2002). In vitro evaluation of the cytotoxic potential of alkylphenols from Ginkgo biloba L. Toxicology 177:167-177.
55. Hellum BH, Nilsen OG. (2008). In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products. Basic Clin Pharmacol Toxicol 102:466-475.
56. Herrschaft H, Nacu A, Likhachev S, et al. (2012). Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features: A randomised, placebo-controlled trial to confirm the efficacy and safety of a daily dose of 240 mg. J Psychiatr Res 46:716-723.
57. Hu ZY, Zhao YS, Wu D, Cheng ZN. (2009). Endogenous cortisol 6 betahydroxylation clearance is not an accurate probe for overall cytochrome P450 3A phenotyping in humans. Clin Chim Acta 408: 92-97.
58. Hutzler JM, Balogh LM, Zientek M, et al. (2009). Mechanism-based inactivation of cytochrome P450 2C9 by tienilic acid and (/ )-suprofen: A comparison of kinetics and probe substrate selection. Drug Metab Dispos 37:59-65.
59. Hyland R, Jones BC, Smith DA. (2003). Identification of the cytochrome P450 enzymes involved in the N-oxidation of voriconazole. Drug Metab Dispos 31:540-547.
60. Ihl R, Bachinskaya N, Korczyn AD, et al. (2011). Efficacy and safety of a once-daily formulation of Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features: A randomized controlled trial. Int J Geriatr Psychiatry 26:1186-1194.
61. Imanaga J, Kotegawa T, Imai H, et al. (2011). The effects of the SLCO2B1 c.1457C4T polymorphism and apple juice on the pharmacokinetics of fexofenadine and midazolam in humans. Pharmacogenet Genomics 21:84-93.
62. Jager AK, Saaby L. (2011). Flavonoids and the CNS. Molecules 16: 1471-1485.
63. Jefferson JW, Pradko JF, Muir KT. (2005). Bupropion for major depressive disorder: Pharmacokinetic and formulation considerations. Clin Ther 27:1685-1695.
64. Jeu L, Piacenti FJ, Lyakhovetskiy AG, Fung HB. (2003). Voriconazole. Clin Ther 25:1321-1381.
65. Jiang X, Williams KM, Liauw WS, et al. (2005). Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 59:425-432.
66. Jones SA, Moore LB, Shenk JL, et al. (2000). The pregnane X receptor: A promiscuous xenobiotic receptor that has diverged during evolution. Mol Endocrinol 14:27-39.
67. Kalliokoski A, Niemi M. (2009). Impact of OATP transporters on pharmacokinetics. Br J Pharmacol 158:693-705.
68. Kaminsky LS, Zhang ZY. (1997). Human P450 metabolism of warfarin. Pharmacol Ther 73:67-74.
69. Karam WG, Goldstein JA, Lasker JM, Ghanayem BI. (1996). Human CYP2C19 is a major omeprazole 5-hydroxylase, as demonstrated with recombinant cytochrome P450 enzymes. Drug Metab Dispos 24: 1081-1087.
70. Kehr J, Yoshitake S, Ijiri S, et al. (2012). Ginkgo biloba leaf extract (EGb 761) and its specific acylated flavonol constituents increase dopamine and acetylcholine levels in the rat medial prefrontal cortex: Possible implications for the cognitive enhancing properties of EGb 761. Int Psychogeriatr 24:S25-S34.
71. Kim BH, Kim KP, Lim KS, et al. (2010). Influence of Ginkgo biloba extract on the pharmacodynamic effects and pharmacokinetic properties of ticlopidine: An open-label, randomized, two-period, twotreatment, two-sequence, single-dose crossover study in healthy Korean male volunteers. Clin Ther 32:380-390.
72. Kimoto E, Chupka J, Xiao Y, et al. (2011). Characterization of digoxin uptake in sandwich-cultured human hepatocytes. Drug Metab Dispos 39:47-53.
73. Kimura N, Masuda S, Tanihara Y, et al. (2005). Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet 20:379-386.
74. Konig J. (2011). Uptake transporters of the human OATP family: Molecular characteristics, substrates, their role in drug-drug interactions, and functional consequences of polymorphisms. Handb Exp Pharmacol 201:1-28.
75. Kressmann S, Biber A, Wonnemann M, et al. (2002a). Influence of pharmaceutical quality on the bioavailability of active components from Ginkgo biloba preparations. J Pharm Pharmacol 54:1507-1514.
76. Kressmann S, Muller WE, Blume HH. (2002b). Pharmaceutical quality of different Ginkgo biloba brands. J Pharm Pharmacol 54:661-669.
77. Kudolo GB, Wang W, Javors M, Blodgett J. (2006). The effect of the ingestion of Ginkgo biloba extract (EGb 761) on the pharmacokinetics of metformin in non-diabetic and type 2 diabetic subjects-A double blind placebo-controlled, crossover study. Clin Nutr 25:606-616.
78. Kullak-Ublick GA, Ismair MG, Stieger B, et al. (2001). Organic aniontransporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology 120: 525-533.
79. Kupiec T, Raj V. (2005). Fatal seizures due to potential herb-drug interactions with Ginkgo biloba. J Anal Toxicol 29:755-758.
80. Laine JE, Auriola S, Pasanen M, Juvonen RO. (2009). Acetaminophen bioactivation by human cytochrome P450 enzymes and animal microsomes. Xenobiotica 39:11-21.
81. Lau AJ, Yang G, Rajaraman G, et al. (2010). Human pregnane X receptor agonism by Ginkgo biloba extract: Assessment of the role of individual ginkgolides. J Pharmacol Exp Ther 335:771-780.
82. Lei HP, JiW, Lin J, et al. (2009a). Effects of Ginkgo biloba extract on the pharmacokinetics of bupropion in healthy volunteers. Br J Clin Pharmacol 68:201-206.
83. Lei HP, Wang G, Wang LS, et al. (2009b). Lack of effect of Ginkgo biloba on voriconazole pharmacokinetics in Chinese volunteers identified as CYP2C19 poor and extensive metabolizers. Ann Pharmacother 43:726-731.
84. Li L, Stanton JD, Tolson AH, et al. (2009). Bioactive terpenoids and flavonoids from Ginkgo biloba extract induce the expression of hepatic drug-metabolizing enzymes through pregnane X receptor, constitutive androstane receptor, and aryl hydrocarbon receptormediated pathways. Pharm Res 26:872-882.
85. Liu Z, Hu M. (2007). Natural polyphenol disposition via coupled metabolic pathways. Expert Opin Drug Metab Toxicol 3:389-406.
86. Lu WJ, Huang JD, Lai. ML. (2006). The effects of ergoloid mesylates and Ginkgo biloba on the pharmacokinetics of ticlopidine. J Clin Pharmacol 46:628-634.
87. Ma JD, Tsunoda SM, Bertino Jr JS, et al. (2010). Evaluation of in vivo P-glycoprotein phenotyping probes: A need for validation. Clin Pharmacokinet 49:223-237.
88. Madsen H, Enggaard TP, Hansen LL, et al. (2001). Fluvoxamine inhibits the CYP2C9 catalyzed biotransformation of tolbutamide. Clin Pharmacol Ther 69:41-47.
89. Mandery K, Bujok K, Schmidt I, et al. (2010). Influence of the flavonoids apigenin, kaempferol, and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1. Biochem Pharmacol 80:1746-1753.
90. Markowitz JS, DeVane CL, Lewis JG, et al. (2005). Effect of Ginkgo biloba extract on plasma steroid concentrations in healthy volunteers: A pilot study. Pharmacotherapy 25:1337-1340.
91. Markowitz JS, Donovan JL, DeVane CL, et al. (2003). Multiple-dose administration of Ginkgo biloba did not affect cytochrome P-450 2D6 or 3A4 activity in normal volunteers. J Clin Psychopharmacol 23: 576-581.
92. Masubuchi Y, Hosokawa S, Horie T, et al. (1994). Cytochrome P450 isozymes involved in propranolol metabolism in human liver microsomes. The role of CYP2D6 as ring-hydroxylase and CYP1A2 as N-desisopropylase. Drug Metab Dispos 22:909-915.
93. Mathews JM, Etheridge AS, Valentine JL, et al. (2005). Pharmacokinetics and disposition of the kavalactone kawain: Interaction with kava extract and kavalactones in vivo and in vitro. Drug Metab Dispos 33:1555-1563.
94. Matsushima S, Maeda K, Hayashi H, et al. (2008). Involvement of multiple efflux transporters in hepatic disposition of fexofenadine. Mol Pharmacol 73:1474-1483.
95. Mauri P, De Palma A, Pozzi F, et al. (2006). LC-MS characterization of terpene lactones in plasma of experimental animals treated with Ginkgo biloba extracts: Correlation with pharmacological activity. J Pharm Biomed Anal 40:763-768.
96. Mauro VF, Mauro LS, Kleshinski JF, et al. (2003). Impact of Ginkgo biloba on the pharmacokinetics of digoxin. Am J Ther 10:247-251.
97. McKenna DJ, Jones K, Hughes K. (2001). Efficacy, safety, and use of Ginkgo biloba in clinical and preclinical applications. Altern Ther Health Med 7:70-90.
98. Miners JO, Birkett DJ. (1998). Cytochrome P4502C9: An enzyme of major importance in human drug metabolism. Br J Clin Pharmacol 45: 525-538.
99. Miura M, Kagaya H, Satoh S, et al. (2008). Influence of drug transporters and UGT polymorphisms on pharmacokinetics of phenolic glucuronide metabolite of mycophenolic acid in Japanese renal transplant recipients. Ther Drug Monit 30:559-564.
100. Miura M, Satoh S, Inoue K, et al. (2007). Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol 63:1161-1169.
101. Mohamed MF, Frye RF. (2010). Inhibition of intestinal and hepatic glucuronidation of mycophenolic acid by Ginkgo biloba extract and flavonoids. Drug Metab Dispos 38:270-275.
102. Mohutsky MA, Anderson GD, Miller JW, Elmer GW. (2006). Ginkgo biloba: Evaluation of CYP2C9 drug interactions in vitro and in vivo. Am J Ther 13:24-31.
103. Nabekura T, Yamaki T, Ueno K, Kitagawa S. (2008). Inhibition of P-glycoprotein and multidrug resistance protein 1 by dietary phytochemicals. Cancer Chemother Pharmacol 62:867-873.
104. Naccarato M, Yoong D, Gough K. (2012). A potential drug-herbal interaction between Ginkgo biloba and Efavirenz. J Int Assoc Physicians AIDS Care 11:98-100.
105. Nare B, Prichard RK, Georges E. (1994). Characterization of rhodamine 123 binding to P-glycoprotein in human multidrug-resistant cells. Mol Pharmacol 45:1145-1152.
106. Newton DJ, Wang RW, Lu AY. (1995). Cytochrome P450 inhibitors. Evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab Dispos 23:154-158.
107. Nieder M. (1991). Pharmakokinetik der Ginkgo-Flavonole im Plasma. Munch Med Wschr 133:S61-62.
108. Nowack R, Andrassy J, Fischereder M, Unger M. (2009). Effects of dietary factors on drug transport and metabolism: The impact on dosage guidelines in transplant patients. Clin Pharmacol Ther 85: 439-443.
109. Numa AM, Abbott FS, Chang TK. (2007). Effect of Ginkgo biloba extract on oxidative metabolism of valproic acid in hepatic microsomes from donors with the CYP2C91/1 genotype. Can J Physiol Pharmacol 85:848-855.
110. Obach RS, Walsky RL, Venkatakrishnan K, et al. (2006). The utility of in vitro cytochrome P450 inhibition data in the prediction of drug-drug interactions. J Pharmacol Exp Ther 316:336-348.
111. Ogburn ET, Jones DR, Masters AR, et al. (2010). Efavirenz primary and secondary metabolism in vitro and in vivo: Identification of novel metabolic pathways and cytochrome P450 2A6 as the principal catalyst of efavirenz 7-hydroxylation. Drug Metab Dispos 38: 1218-1229.
112. Ohnishi N, Kusuhara M, Yoshioka M, et al. (2003). Studies on interactions between functional foods or dietary supplements and medicines. I. Effects of Ginkgo biloba leaf extract on the pharmacokinetics of diltiazem in rats. Biol Pharm Bull 26:1315-1320.
113. Pascussi JM, Gerbal-Chaloin S, Duret C, et al. (2008). The tangle of nuclear receptors that controls xenobiotic metabolism and transport: Crosstalk and consequences. Annu Rev Pharmacol Toxicol 48:1-32.
114. PharmEUR. (1999). Ginkgo Dry Extract, standardized. Pharmeuropa 11: 333-337.
115. Picard N, Ratanasavanh D, Premaud A, et al. (2005). Identification of the UDP-glucuronosyltransferase isoforms involved in mycophenolic acid phase II metabolism. Drug Metab Dispos 33:139-146.
116. Picard N, Yee SW, Woillard JB, et al. (2010). The role of organic aniontransporting polypeptides and their common genetic variants in mycophenolic acid pharmacokinetics. Clin Pharmacol Ther 87: 100-108.
117. Pietta PG, Gardana C, Mauri PL. (1997). Identification of Gingko biloba flavonol metabolites after oral administration to humans. J Chromatogr B Biomed Sci Appl 693:249-255.
118. Pietta PG, Gardana C, Mauri PL, et al. (1995). Identification of flavonoid metabolites after oral administration to rats of a Ginkgo biloba extract. J Chromatogr B Biomed Appl 673:75-80.
119. Prickett KS, Baillie TA. (1984). Metabolism of valproic acid by hepatic microsomal cytochrome P-450. Biochem Biophys Res Commun 122: 1166-1173.
120. Rajaraman G, Chen J, Chang TK. (2006). Ginkgolide A contributes to the potentiation of acetaminophen toxicity by Ginkgo biloba extract in primary cultures of rat hepatocytes. Toxicol Appl Pharmacol 217: 225-233.
121. Rangel-Ordonez L, Noldner M, Schubert-Zsilavecz M, Wurglics M. (2010). Plasma levels and distribution of flavonoids in rat brain after single and repeated doses of standardized Ginkgo biloba extract EGb 761. Planta Med 76:1683-1690.
122. Rengelshausen J, Banfield M, Riedel KD, et al. (2005). Opposite effects of short-term and long-term St John's wort intake on voriconazole pharmacokinetics. Clin Pharmacol Ther 78:25-33.
123. Rettie AE, Korzekwa KR, Kunze KL, et al. (1992). Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: A role for P-450 2C9 in the etiology of (S)-warfarin-drug interactions. Chem Res Toxicol 5:54-59.
124. Rettie AE, Rettenmeier AW, Howald WN, Baillie TA. (1987). Cytochrome P-450-catalyzed formation of delta 4-VPA, a toxic metabolite of valproic acid. Science 235:890-893.
125. Robertson SM, Davey RT, Voell J, et al. (2008). Effect of Ginkgo biloba extract on lopinavir, midazolam and fexofenadine pharmacokinetics in healthy subjects. Curr Med Res Opin 24:591-599.
126. Rotzinger S, Fang J, Baker GB. (1998). Trazodone is metabolized to mchlorophenylpiperazine by CYP3A4 from human sources. Drug Metab Dispos 26:572-575.
127. Sasaki K, Wada K, Hatta S, et al. (1997). Bilobalide, a constituent of Ginkgo biloba L, potentiates drug-metabolizing enzyme activities in mice: Possible mechanism for anticonvulsant activity against 4-Omethylpyridoxine- induced convulsions. Res Commun Mol Pathol Pharmacol 96:45-56.
128. Satsu H, Hiura Y, Mochizuki K, et al. (2008). Activation of pregnane X receptor and induction of MDR1 by dietary phytochemicals. J Agric Food Chem 56:5366-5373.
129. Schmider J, Greenblatt. DJ, von Moltke LL, Shader RI. (1996). Relationship of in vitro data on drug metabolism to in vivo pharmacokinetics and drug interactions: Implications for diazepam disposition in humans. J Clin Psychopharmacol 16:267-272.
130. Shi C, Liu J, Wu F, Yew DT. (2010). Ginkgo biloba extract in Alzheimer's disease: From action mechanisms to medical practice. Int J Mol Sci 11:107-123.
131. Shinozuka K, Umegaki K, Kubota Y, et al. (2002). Feeding of Ginkgo biloba extract (GBE) enhances gene expression of hepatic cytochrome P-450 and attenuates the hypotensive effect of nicardipine in rats. Life Sci 70:2783-2792.
132. Shirasaka Y, Suzuki K, Nakanishi T, Tamai I. (2011). Differential effect of grapefruit juice on intestinal absorption of statins due to inhibition of organic anion transporting polypeptide and/or P-glycoprotein. J Pharm Sci 100:3843-3853.
133. Shord SS, Cavallari LH, Viana MA, et al. (2008). Cytochrome P450 2C9 mediated metabolism in people with and without cancer. Int J Clin Pharmacol Ther 46:365-374.
134. Siegers CP. (1999). Cytotoxicity of alkylphenols from Ginkgo biloba. Phytomedicine 6:281-283.
135. Singh B, Kaur P, Gopichand Singh RD, Ahuja PS. (2008). Biology and chemistry of Ginkgo biloba. Fitoterapia 79:401-418.
136. Song J, Fang G, Zhang Y, et al. (2010). Fingerprint analysis of Ginkgo biloba leaves and related health foods by high-performance liquid chromatography/electrospray ionization-mass spectrometry. J AOAC Int 93:1798-1805.
137. Spahn-Langguth H, Baktir G, Radschuweit A, et al. (1998). P-glycoprotein transporters and the gastrointestinal tract: Evaluation of the potential in vivo relevance of in vitro data employing talinolol as model compound. Int J Clin Pharmacol Ther 36:16-24.
138. Sugiyama T, Kubota Y, Shinozuka K, et al. (2004). Ginkgo biloba extract modifies hypoglycemic action of tolbutamide via hepatic cytochrome P450 mediated mechanism in aged rats. Life Sci 75: 1113-1122.
139. Taki Y, Hagiwara E, Hirose C, et al. (2011). Effects of Ginkgo biloba extract on the pharmacokinetics and pharmacodynamics of tolbutamide in protein-restricted rats. J Pharm Pharmacol 63:1238-1243.
140. Taki Y, Yamazaki Y, Shimura F, et al. (2009). Time-dependent induction of hepatic cytochrome P450 enzyme activity and mRNA expression by bilobalide in rats. J Pharmacol Sci 109:459-462.
141. Taki Y, Yokotani K, Yamada S, et al. (2012). Ginkgo biloba extract attenuates warfarin-mediated anticoagulation through induction of hepatic cytochrome P450 enzymes by bilobalide in mice. Phytomedicine 19:177-182.
142. Tamasi V, Juvan P, Beer M, et al. (2009). Transcriptional activation of PPAR alpha by phenobarbital in the absence of CAR and PXR. Mol Pharm 6:1573-1581.
143. Tang J, Sun J, Zhang Y, et al. (2007). Herb-drug interactions: Effect of Ginkgo biloba extract on the pharmacokinetics of theophylline in rats. Food Chem Toxicol 45:2441-2445.
144. Tang D, Yang D, Tang A, et al. (2010). Simultaneous chemical fingerprint and quantitative analysis of Ginkgo biloba extract by HPLC-DAD. Anal Bioanal Chem 396:3087-3095.
145. Taub ME, Mease K, Sane RS, et al. (2011). Digoxin is not a substrate for organic anion-transporting polypeptide transporters OATP1A2, OATP1B1, OATP1B3, and OATP2B1 but is a substrate for a sodiumdependent transporter expressed in HEK293 cells. Drug Metab Dispos 39:2093-2102.
146. Tiseo PJ, Perdomo CA, Friedhoff LT. (1998). Metabolism and elimination of 14C-donepezil in healthy volunteers: A single-dose study. Br J Clin Pharmacol 46:19-24.
147. Uchida S, Yamada H, Li XD, et al. (2006). Effects of Ginkgo biloba extract on pharmacokinetics and pharmacodynamics of tolbutamide and midazolam in healthy volunteers. J Clin Pharmacol 46: 1290-1298.
148. Umegaki K, Taki Y, Endoh K, et al. (2007). Bilobalide in Ginkgo biloba extract is a major substance inducing hepatic CYPs. J Pharm Pharmacol 59:871-877.
149. Unger M. (2010). Pharmacokinetic drug interactions by herbal drugs: Critical evaluation and clinical relevance. Wien Med Wochenschr 160:571-577.
150. Unger M. (2011). Pharmacokinetic drug interactions between anticancer therapeutics and drugs of complementary medicine: Mechanisms and clinical relevance. Forsch Komplementmed 18: 213-218.
151. Unger M, Frank A. (2004). Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 18: 2273-2281.
152. Unger M, Holzgrabe U, Jacobsen W, et al. (2002). Inhibition of cytochrome P450 3A4 by extracts and kavalactones of Piper methysticum (Kava-Kava). Planta Med 68:1055-1058.
153. Unger M, Laug S, Holzgrabe U. (2005). Capillary zone electrophoresis as a tool for the quality control of goldenseal extracts. Electrophoresis 26:2430-2436.
154. USP. (2008). Powdered ginkgo extract. In: The United States Pharmacopeial Convention Inc. Monograph Powdered Ginkgo Extract USP 32:1019-1021.
155. van Beek TA, Montoro P. (2009). Chemical analysis and quality control of Ginkgo biloba leaves, extracts, and phytopharmaceuticals. J Chromatogr A 1216:2002-2032.
156. Veronese ME, Miners JO, Randles D, et al. (1990). Validation of the tolbutamide metabolic ratio for population screening with use of sulfaphenazole to produce model phenotypic poor metabolizers. Clin Pharmacol Ther 47:403-411.
157. Verschraagen M, Koks CH, Schellens JH, Beijnen J. (1999). P-glycoprotein system as a determinant of drug interactions: The case of digoxin-verapamil. Pharmacol Res 40:301-306.
158. von Moltke LL, Weemhoff JL, Bedir E, et al. (2004). Inhibition of human cytochromes P450 by components of Ginkgo biloba. J Pharm Pharmacol 56:1039-1044.
159. von Moltke LL, Weemhoff JL, Perloff MD, et al. (2002). Effect of zolpidem on human cytochrome P450 activity, and on transport mediated by P-glycoprotein. Biopharm Drug Dispos 23: 361-367.
160. Walsky RL, Obach RS. (2004). Validated assays for human cytochrome P450 activities. Drug Metab Dispos 32:647-660.
161. Wang DL, Liang Y, Chen WD, et al. (2008a). Identification of ginkgolide B metabolites in urine and rat liver cytochrome P450 enzymes responsible for their formation in vitro. Acta Pharmacol Sin 29:376-384.
162. Wang J, Figurski M, Shaw LM, Burckart GJ. (2008b). The impact of P-glycoprotein and Mrp2 on mycophenolic acid levels in mice. Transpl Immunol 19:192-196.
163. Watanabe CM, Wolffram S, Ader P, et al. (2001). The in vivo neuromodulatory effects of the herbal medicine Ginkgo biloba. Proc Natl Acad Sci USA 98:6577-6580.
164. Watkins PB. (1994). Noninvasive tests of CYP3A enzymes. Pharmacogenetics 4:171-184.
165. Weiss J, Ten Hoevel MM, Burhenne J, et al. (2009). CYP2C19 genotype is a major factor contributing to the highly variable pharmacokinetics of voriconazole. J Clin Pharmacol 49:196-204.
166. WHO. (1999). Folium Ginkgo. In: WHO. WHO monographs on selected medicinal plants, volume 1. Geneva: World Health Organization, 154-167.
167. Wiegman DJ, Brinkman K, Franssen EJ. (2009). Interaction of Ginkgo biloba with efavirenz. AIDS 23:1184-1185.
168. Williams JA, Hyland R, Jones BC, et al. (2004). Drug-drug interactions for UDP-glucuronosyltransferase substrates: A pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos 32:1201-1208.
169. Winzer R, Langmann P, Zilly M, et al. (2003). No influence of the P-glycoprotein genotype (MDR1 C3435T) on plasma levels of lopinavir and efavirenz during antiretroviral treatment. Eur J Med Res 8:531-534.
170. Woelkart K, Feizlmayr E, Dittrich P, et al. (2010). Pharmacokinetics of bilobalide, ginkgolide A and B after administration of three different Ginkgo biloba L. preparations in humans. Phytother Res 24:445-450.
171. Xie J, Ding C, Ge Q, et al. (2008). Simultaneous determination of ginkgolides A, B, C and bilobalide in plasma by LC-MS/MS and its application to the pharmacokinetic study of Ginkgo biloba extract in rats. J Chromatogr B 864:87-94.
172. Xin HW, Wu XC, Li Q, et al. (2009). Effects of Schisandra sphenanthera extract on the pharmacokinetics of midazolam in healthy volunteers. Br J Clin Pharmacol 67:541-546.
173. Xin HW, Wu XC, Li Q, et al. (2007). Effects of Schisandra sphenanthera
174. Yale SH, Glurich I. (2005). Analysis of the inhibitory potential of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9. J Altern Complement Med 11:433-439.
175. Yamazaki H, Inoue K, Shaw PM, et al. (1997). Different contributions of cytochrome P450 2C19 and 3A4 in the oxidation of omeprazole by human liver microsomes: Effects of contents of these two forms in individual human samples. J Pharmacol Exp Ther 283:434-442.
176. Yang TJ, Shou M, Korzekwa KR, et al. (1998). Role of cDNA-expressed human cytochromes P450 in the metabolism of diazepam. Biochem Pharmacol 55:889-896.
177. Yang XF, Wang NP, Lu WH, Zeng FD. (2003). Effects of Ginkgo biloba extract and tanshinone on cytochrome P-450 isozymes and glutathione transferase in rats. Acta Pharmacol Sin 24:1033-1038.
178. Yasui-Furukori N, Furukori H, Kaneda A, et al. (2004). The effects of Ginkgo biloba extracts on the pharmacokinetics and pharmacodynamics of donepezil. J Clin Pharmacol 44:538-542.
179. Yeung EY, Sueyoshi T, Negishi M, Chang TK. (2008). Identification of Ginkgo biloba as a novel activator of pregnane X receptor. Drug Metab Dispos 36:2270-2276.
180. Yin OQ, Lam SS, Lo CM, Chow MS. (2004a). Rapid determination of five probe drugs and their metabolites in human plasma and urine by liquid chromatography/tandem mass spectrometry: Application to cytochrome P450 phenotyping studies. Rapid Commun Mass Spectrom 18:2921-2933.
181. Yin OQ, Tomlinson B, Waye MM, et al. (2004b). Pharmacogenetics and herb-drug interactions: Experience with Ginkgo biloba and omeprazole. Pharmacogenetics 14:841-850.
182. Yoshioka M, Ohnishi N, Koishi T, et al. (2004). Studies on interactions between functional foods or dietary supplements and medicines. IV. Effects of Ginkgo biloba leaf extract on the pharmacokinetics and pharmacodynamics of nifedipine in healthy volunteers. Biol Pharm Bull 27:2006-2009.
183. Yu C, Chai X, Yu L, et al. (2011). Identification of novel pregnane X receptor activators from traditional Chinese medicines. J Ethnopharmacol 136:137-143.
184. Yueh MF, Mellon PL, Tukey RH. (2011). Inhibition of human UGT2B7 gene expression in transgenic mice by the constitutive androstane receptor. Mol Pharmacol 79:1053-1060.
185. adoyan G, Rokitta D, Klement S, et al. (2012). Effect of Ginkgo biloba special extract EGb 761 on human cytochrome P450 activity: A cocktail interaction study in healthy volunteers. Eur J Clin Pharmacol 68:553-560.
186. Zhao LZ, Huang M, Chen J, et al. (2006). Induction of propranolol metabolism by Ginkgo biloba extract EGb 761 in rats. Curr Drug Metab 7:577-587.
187. Zhou C, Poulton EJ, Grun F, et al. (2007). The dietary isothiocyanate sulforaphane is an antagonist of the human steroid and xenobiotic nuclear receptor. Mol Pharmacol 71:220-229.
188. Zhou HH. (2001). CYP2C19 genotype determines enzyme activity and inducibility of S-mephenytoin hydroxylase. Clin Chim Acta 313: 203-208.
189. Zhou S, Chan E, Li SC, et al. (2004). Predicting pharmacokinetic herb-drug interactions. Drug Metabol Drug Interact 20:143-158.
190. Zou L, Harkey MR, Henderson GL. (2002). Effects of intrinsic fluorescence and quenching on fluorescence-based screening of natural products. Phytomedicine 9:263-267.
191. Zuo XC, Zhang BK, Jia SJ, et al. (2010). Effects of Ginkgo biloba extracts on diazepam metabolism: A pharmacokinetic study in healthy Chinese male subjects. Eur J Clin Pharmacol 66: 503-509.