Hostname: page-component-6766d58669-bkrcr Total loading time: 0 Render date: 2026-05-21T12:47:59.248Z Has data issue: false hasContentIssue false
  • English
  • Français

Herb-Drug Interactions: Focus on Pharmacokinetics

Published online by Cambridge University Press:  07 November 2014

Jerry M. Cott
Get access Rights & Permissions [Opens in a new window]

Abstract

Recent literature regarding drug-drug, herb-drug, and food-drug interactions must not be ignored; nor can they always be taken at face value. Studies have shown that St. John's wort (SJW) (Hypericum perforatum) can reduce plasma levels of indinavir, cyclosporin, digoxin, and possibly other drugs as well. Current knowledge regarding the metabolism of these medications suggests that the cytochrome P450 (CYP) drug metabolizing enzyme systems cannot account for all these effects. It has been reported that the P-glycoprotein (Pgp) transmembrane pump is also induced by SJW. Medications that are substrates of both CYP 3A4 a Pgp are of particular concern and may pose special interaction risks when combined with certain foods or botanical products such as SJW.

Information

Type
Feature Articles
Information
CNS Spectrums , Volume 6 , Issue 10: Empirical Evaluations of Selected Herbal Remedies , October 2001 , pp. 827 - 832
Copyright
Copyright © Cambridge University Press 2001

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

REFERENCES

1. Fugh-Berman, A, Cott, JM. Dietary supplements and natural products as psychotherapeutic agents. Psychosom Med. 1999;61:712–728.Google Scholar
2. Wong, AH, Smith, M, Boon, HS. Herbal remedies in psychiatric practice. Arch Gen Psychiatry. 1998;55:1033–1044.Google Scholar
3. De Smet, PA, Brouwers, JR. Pharmacokinetic evaluation of herbal remedies: basic introduction, applicability, current status and regulatory needs. Clin Pharmacokinet. 1997;32:427–436.CrossRefGoogle ScholarPubMed
4. Hardman, JG, Limbird, LE, Molinoff, PB et al. , eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York, NY: McGraw-Hill; 1996:11–14.Google Scholar
5. Caraco, Y. Genetic determinants of drug responsiveness and drug interactions. Ther Drug Monk. 1998;20:517–524.Google Scholar
6. Mohri, K, Uesawa, Y, Sagawa, K-I. Effects of long-term grapefruit juice ingestion on nifedipine pharmacokinetics: induction of rat hepatic P-450 by grapefruit juice. Drug Metab Dispos. 2000;28:482–486.Google ScholarPubMed
7. Kim, HJ, Chun, YJ, Park, JD, et al. Protection of rat liver microsomes against carbon tetrachloride-induced lipid peroxidation by red ginseng saponin through cytochrome P450 inhibition. Planta Med. 1997;63:415–418.Google Scholar
8. Tirillini, B. Grapefruit: the last decade acquisitions. Fitoterapia.2000;71 (suppl 1):S29–S37.Google Scholar
9. Ohnishi, A, Matsuo, H, Yamada, S, et al. Effect of furanocoumarin derivatives in grapefruit juice on the uptake of vinblastine by Caco-2 cells and on the activity of cytochrome P450 3A4. Br J Pharmacol. 2000;130:1369–1377.Google Scholar
10. Obermeier, MT, White, RE, Yang, CS. Effects of bioflavonoids on hepatic P450 activities. Xenobiotica. 1995;25:575–584.CrossRefGoogle ScholarPubMed
11. Henderson, MC, Miranda, CL, Stevens, JF, et al. In vitro inhibition of human P450 enzymes by prenylated flavonoids from hops, Humulus lupulus. Xenobiotica. 2000;30:235–251.Google Scholar
12. Ueng, YF, Shyu, CC, Lin, YL, et al. Effects of baicalein and wogonin on drug-metabolizing enzymes in C57BL/6J mice. Life Sci. 2000;67:2189–2200.CrossRefGoogle ScholarPubMed
13. Li, Y, Wang, E, Patten, CJ, et al. Effects of flavonoids on cytochrome P450-dependent acetaminophen metabolism in rats and human liver microsomes. Drug Metab Dispos. 1994;22:566–571.Google Scholar
14. Lown, KS, Bailey, DG, Fontana, RJ, et al. Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. J Clin Invest. 1997;99:2545–2553.Google Scholar
15. Fuhr, U. Drug interactions with grapefruit juice: extent, probable mechanism and clinical relevance. Drug Saf. 1998;18:251–272.Google Scholar
16. Ozdemir, M, Aktan, Y, Boydag, BS, et al. Interaction between grapefruit juice and diazepam in humans. Eur J Drug Metab Pharmacokinet. 1998;23:55–59.Google Scholar
17. Kail, MA, Vang, O, Clausen, J. Effects of dietary broccoli on human in vivo drug metabolizing enzymes: evaluation of caffeine, oestrone and chlorzoxazone metabolism. Carcinogenesis. 1996;17:793–799.Google Scholar
18. Fontana, RJ, Lown, KS, Paine, MF, et al. Effects of a char-grilled meat diet on expression of CYP3A, CYP1A, and P-glycoprotein levels in healthy volunteers. Gastroenterology. 1999;117:89–98.Google Scholar
19. Obach, RS. Inhibition of human cytochrome P450 enzymes by constituents of St. John's wort, an herbal preparation used in the treatment of depression. J Pharmacol Exp Ther. 2000;294:88–95.Google ScholarPubMed
20. Biber, A, Fischer, H, Romer, A, et al. Oral bioavailability of hyperforin from hypericum extracts in rats and human volunteers. Pharmacopsychiatry. 1998;31(suppl 1):36–43.Google Scholar
21. Moor, LB, Goodwin, B, Jones, SA, et al. St. John's wort induces hepatic drug metabolism through activation of the pregname X receptor. Acad Sci USA. 2000;97:7500–7502.Google Scholar
22. Roby, CA, Anderson, GD, Kantor, E, et al. St John's wort: effect on CYP3A4 activity. Clin Pharmacol Ther. 2000;67:451–457.Google Scholar
23. Markowitz, JS, DeVane, CL, Boulton, DW, et al. Effect of St. John's wort (Hypericum perforatum) on cytochrome P-450 2D6 and 3A4 activity in healthy volunteers. Life Sci. 2000;66:PL133–PL139.CrossRefGoogle ScholarPubMed
24. Ereshefsky, B, Gewertz, N, Lam, YWF, et al. Determination of SJW differential metabolism at CYP2D6 and CYP3A4 using dextromethorphan probe technology. In: Abstracts from the 39th Annual Meeting of the New Clinical Drug Evaluation Unit; June 1999;130. Boca Raton, Fl.Google Scholar
25. Gewertz, N, Ereshefsky, B, Lam, YWF, et al. Determination of differential effects of St. John's wort on the CYP1A2 and NAT2 metabolic pathways using caffeine probe technology. In: Abstracts from the 39th Annual Meeting of the New Clinical Drug Evaluation Unit. 1999;131. Boca Raton, Fl.Google Scholar
26. Johnstone, RW, Ruefli, AA, Smyth, MJ. Multiple physiological functions for multidrug transporter P-glycoprotein? Trends Biochem Sci. 2000;25:1–6.CrossRefGoogle ScholarPubMed
27. Yu, D. K.The contribution of P-glycoprotein to pharmacokinetic drug-drug interactions. J Clin Pharmacol. 1999;39:1203–1211.Google Scholar
28. Tanigawara, Y. Role of P-glycoprotein in drug disposition. Ther Drug Monit. 2000;22:137–140.Google Scholar
29. Sugiyama, Y, Kusuhara, H, Suzuki, H. Kinetic and biochemical analysis of carrier-mediated efflux of drugs through the blood-brain and blood-cerebrospinal fluid barriers: importance in the drug delivery to the brain. J Control Release. 1999;62:179–186.CrossRefGoogle ScholarPubMed
30. Drach, J, Gsur, A, Hamilton, G, et al. Involvement of P-glycoprotein in the transmembrane transport of interleukin-2 (IL-2), IL-4, and interferongamma in normal human T lymphocytes. Blood. 1996;88:1747–1754.Google Scholar
31. Kim, RB, Wandel, C, Leake, B, et al. Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm Res. 1999;16:408–414.Google ScholarPubMed
32. Hochman, JH, Chiba, M, Nishime, J, et al. Influence of P-glycoprotein on the transport and metabolism of indinavir in Caco-2 cells expressing cytochrome P-450 3A4. J Pharmacol Exp Ther. 2000;292:310–318.Google Scholar
33. Wartenberg, M, Fischer, K, Hescheler, J, et al. Redox regulation of P-glycoprotein-mediated multidrug resistance in multicellular prostate tumor spheroids. Int J Cancer. 2000;85:267–274.Google Scholar
34. Maitrejean, M, Comte, G, Barron, D, et al. The flavanolignan silybin and its hemisynthetic derivatives: a novel series of potential modulators of P-glycoprotein. Bioorg Med Chem Lett. 2000;10:157–160.Google Scholar
35. Plouzek, CA, Ciolino, HP, Clarke, R, et al. Inhibition of P-glycoprotein activity and reversal of multidrug resistance in vitro by rosemary extract. Eur J Cancer. 1999;35:1541–1545.Google Scholar
36. Offord, EA, Mace, K, Avanti, O, et al. Mechanisms involved in the chemoprotective effects of rosemary extract studied in human liver and bronchial cells. Cancer Lett. 1997;114:275–281.Google Scholar
37. Takanaga, H, Ohnishi, A, Yamada, S, et al. Polymethoxylated flavones inorange juice are inhibitors of P-glycoprotein but not cytochrome P450 3M. J Pharmacol Exp Ther. 2000;293:230–236.Google Scholar
38. Bock, KW, Eckle, T, Ouzzine, M, et al. Coordinate induction by antioxidants of UDP-glucuronosyltransferase UGT1A6 and the apical conjugate export pump MRP2 (multidrug resistance protein 2) in Caco-2 cells. Biochem Pharmacol. 2000;59:467–470.CrossRefGoogle ScholarPubMed
39. Dürr, D, Stieger, B, Kullak-Ublick, GA, et al. St John's wort induces intestinal P-glycoprotein/MDRl and intestinal and hepatic CYP3A4. Clin Pharmacol Ther. 2000;68:598–604.CrossRefGoogle ScholarPubMed
40. Cott, JM. In vitro receptor binding and enzyme inhibition by Hypericum perforatum extract. Pharmacopsychiatry. 1997;30(suppl. 2):108–112.Google Scholar
41. Müller, WE, Rolli, M, Schäfer, C, et al. Effects of Hypericum extract (LI 160) in biochemical models of antidepressant activity. Pharmacopsychiatry. 1997;30(suppl 2):102–107.Google Scholar
42. Gobbi, M, Valle, FD, Ciapparelli, C, et al. Hypericum perforatum L. extract does not inhibit 5-HT transporter in rat brain cortex. Naunyn Schmiedebergs Arch Pharmacol. 1999;360:262–269.CrossRefGoogle Scholar
43. Upton, R, Graff, A, Williamson, E, et al. American Herbal Pharmacopoeia and Therapeutic Compendium on St. John's wort Hypericum perforatum: Quality control, analytical and therapeutic monograph. HerbalGram. 1997;40 (suppl):1–32.Google Scholar
44. Ruschitzka, F, Meier, PJ, Turina, M, et al. Acute heart transplant rejection due to Saint John's wort. Lancet. 2000;355:548–549.CrossRefGoogle ScholarPubMed
45. Barone, GW, Gurley, BJ, Ketel, BL, et al. Drug interaction between St. John's wort and cyclosporine. Ann Pharmacother. 2000;34:1013–1016.Google Scholar
46. Lown, KS, Mayo, RR, Leichtman, AB, et al. Role of intestinal P-glycoprotein (mdrl) in interpatient variation in the oral bioavailability of cyclosporine. Clin Pharmacol Ther. 1997;62:248–260.Google Scholar
47. Johne, A, Brockmoller, J, Bauer, S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St. John's wort (Hypericum perforatum). Clin Pharmacol Ther. 1999;66:338–345.Google Scholar
48. Piscitelli, SC, Burstein, AH, Chaitt, D, et al. Indinavir concentrations and St. John's wort. Lancet. 2000;355:547–548.Google Scholar
49. Choo, EF, Leake, B, Wandel, C, et al. Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab Dispos. 2000;28:655–660.Google Scholar
50. Maurer, A, Johne, A, Bauer, S, et al. Interaction of St. John's wort extract with phenprocoumon. Eur J Clin Pharmacol. 1999;55:A22.Google Scholar
51. Yue, Q-Y, Bergquist, C, Gerden, B. Safety of St. John's wort (Hypericum perforatum). Lancet. 2000;355:576–577.Google Scholar
52. Bano, G, Raina, RK, Zutshi, U, et al. Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers. Eur J Clin Pharmacol. 1991;41:615–617.CrossRefGoogle ScholarPubMed
53. Walter-Sack, I, Klotz, U. Influence of diet and nutritional status on drug metabolism. Clin Pharmacokinet. 1996;31:47–64.Google Scholar
54. Ha, HR, Chen, J, Freiburghaus, AU, et al. Metabolism of theophylline by cDNA-expressed human cytochromes P-450. Br J Clin Pharmacol. 1995;39:321–326.Google Scholar
55. Lee, H, Yeom, H, Kim, YG, et al. Structure-related inhibition of human hepatic caffeine N3-demethylation by naturally occurring flavonoids. Biochem Pharmacol. 1998;55:1369–1375.Google Scholar
56. Nebel, A, Schneider, BJ, Baker, RK, et al. Potential metabolic interaction between St. John's wort and theophylline. Ann Pharmacother. 1999;33:502.Google Scholar
57. Kharasch, ED, Thummel, KE, Mhyre, J, et al. Single-dose disulfiram inhibition of chlorzoxazone metabolism: a clinical probe for P450 2E1. Clin Pharmacol Ther. 1993;53:643–650.Google Scholar
58. Burstein, AH, Horton, RL, Dunn, T, et al. Lack of effect of St John's wWort on carbamazepine pharmacokinetics in healthy volunteers. Clin Pharmacol Ther. 2000;68:605–612.CrossRefGoogle Scholar
59. Braquet, P. Proofs of involvement of PAF-acether in various immune disorders using BN 52021 (ginkgolide B): a powerful PAF-acether antagonist isolated from Ginkgo biloba L. Adv Prostaglandin Thromboxane Leukot Res. 1986;16:179–198.Google ScholarPubMed
60. Rowin, J, Lewis, SL. Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion. Neurology. 1996;46:1775–1776.Google Scholar
61. Rosenblatt, M, Mindel, J. Spontaneous hyphema associated with ingestion of ginkgo biloba extract. N Engl J Med. 1997:336:1108.Google Scholar
62. Vale, S. Subarachnoid haemorrhage associated with ginkgo biloba. Lancet. 1998;352:36.CrossRefGoogle ScholarPubMed
63. Kim, YS, Pyo, MK, Park, KM, et al. Antiplatelet and antithrombotic effects of a combination of ticlopidine and ginkgo biloba ext (EGb 761). Thromb Res. 1998;91:33–38.CrossRefGoogle ScholarPubMed
64. Busse, W. EGb 761 has no effect on bleeding time in human volunteers. Paper presented at: “Nature's Medicine: Potions or Poisons,” College of Pharmacy at Nova Southeastern University; April 6-8, 2001; Davie, Florida.Google Scholar
65. Kudolo, GB. The effect of 3-month ingestion of Ginkgo biloba extract on pancreatic beta-cell function in response to glucose loading in normal glucose tolerant individuals. J Clin Pharmacol. 2000;40:647–654.Google ScholarPubMed
66. Foo, H, Lemon, J. Acute effects of kava, alone or in combination with alcohol, on subjective measures of impairment and intoxication and on cognitive performance. Drug Alcohol Rev. 1997;16:147–155.Google Scholar
67. Jamieson, DD, Duffield, PH. Positive interaction of ethanol and kava resin in mice. Clin Exp Pharmacol Physiol. 1990;17:509–514.Google Scholar
68. Almeida, JC, Grimsley, EW. Coma from the health food store: interaction between kava and alprazolam. Ann Intern Med. 1996;125:940.Google Scholar