Interactions Between Herbs and Anti-infective Medications

Part of the Infectious Disease book series (ID)


Use of complementary and alternative medications (CAM), including herbal supplements, continues to rise throughout the Western world. This includes patients taking anti-infective medications, particularly individuals with HIV infection. A number of herbal supplements have been shown to modulate cytochrome P450 (CYP)-mediated drug metabolism and certain transport proteins, including the efflux transporter P-glycoprotein (P-gp). Most notably, St. John’s wort is a well-described inducer of CYP3A4 and P-gp and can lower the systemic exposure of anti-infective medications metabolized and/or transported by these proteins. Additional herbal supplements such as Echinacea purpurea, Ginkgo biloba, and Panax ginseng also modulate CYP3A4 to a lesser degree. Assessing herbal preparations for their potential to interact with prescription medications is difficult, due to the lack of ingredient standardization between products. Future studies of herb-drug interaction should be conducted in humans, employ a rigorous study design, and use herbal products that are US Pharmacopeia (USP) or otherwise independently verified. Clinicians caring for patients who elect to use CAM should exhibit a nonjudgmental attitude and document the name, manufacturer, dosage, and start and stop dates of all herbal products. Herb-drug interactions should be considered in the face of unexpected toxicity or therapeutic failure.


Complementary and alternative medications (CAM) Herb Herbal supplement St. John’s wort Hyperforin HIV protease inhibitor Cytochrome P450 (CYP) P-Glycoprotein (P-Gp) USP Verified HIV 


  1. 1.
    Eisenberg DM, Davis RB, Ettner SL et al (1998) Trends in alternative medicine use in the United States, 1990–1997. JAMA 280:1569–1575PubMedGoogle Scholar
  2. 2.
    Maria FA, Jahangir V (2010) Use of herbal products and potential interactions in patients with cardiovascular diseases. J Am Coll Cardiol 55:515–525PubMedPubMedCentralGoogle Scholar
  3. 3.
    Jordan SA, Cunningham DG, Marles RJ (2010) Assessment of herbal medicinal products: challenges, and opportunities to increase the knowledge base for safety assessment. Toxicol Appl Pharmacol 243:198–216PubMedGoogle Scholar
  4. 4.
    Dietary Supplement Health and Education Act 1994, Pub. L. 103–417, Sec,1(a), 108 Stat. 4325 (Oct. 25, 1994)Google Scholar
  5. 5.
    US Pharmacopeial Convention For Manufacturers. Available at: manufacturers. Accessed on: 20 Oct 2016
  6. 6.
  7. 7.
    Bent S, Ko R (2004) Commonly used herbal medicines in the United States. Am J Med 116:478–485PubMedGoogle Scholar
  8. 8.
    Michelle LD, Roger BD, Anthony JL, Gloria YY (2014) Complementary and alternative medicine use by US adults with gastrointestinal conditions: results from the 2012 National Health Interview Survey. Am J Gastroenterol 109:1705–1711Google Scholar
  9. 9.
    Maureen G, Maxim T (2013) Complementary and alternative medicine for asthma self-management. Nurs Clin N Am 48:53–149Google Scholar
  10. 10.
    Dreikorn K (2005) Complementary and alternative medicine in urology. BJU Int 96:1177–1184PubMedGoogle Scholar
  11. 11.
    Wu T, Yang X, Zeng X, Poole P (2008) Traditional Chinese medicine in the treatment of acute respiratory tract infections. Respir Med 102:1093–1098PubMedGoogle Scholar
  12. 12.
    Stickel F, Schuppan D (2007) Herbal medicine in the treatment of liver diseases. Dig Liver Dis 39:293–304PubMedGoogle Scholar
  13. 13.
    Chichon PG (2000) Herbs and the common cold. Adv Nurse Pract 8:31–32PubMedGoogle Scholar
  14. 14.
    Littlewood RA, Vanable PA (2008) Complementary and alternative medicine use among HIV-positive people: research synthesis and implications for HIV care. AIDS Care 20:1002–1018PubMedPubMedCentralGoogle Scholar
  15. 15.
    Fairfield KM, Eisenberg DM, Davis RB, Libman H, Phillips RS (1998) Patterns of use, expenditures, and perceived efficacy of complementary and alternative therapies in HIV-infected patients. Arch Intern Med 158:2257–2264PubMedGoogle Scholar
  16. 16.
    Hsiao AF, Wong MD, Kanouse DE et al (2003) Complementary and alternative medicine use and substitution for conventional therapy by HIV-infected patients. J Acquir Immune Defic Syndr 33:157–165PubMedGoogle Scholar
  17. 17.
    Lesley AB, Catherine AF, Mathew DM et al (2016) Complementary medicine use by people living with HIV in Australia- a national survey. Int J STD AIDS 27(1):33–38Google Scholar
  18. 18.
    Armando H, Minerva J, Sara H, Jesús O, Eduardo S (2009) Use of alternative / complementary therapy in HIV seropositive patients. Rev Med Inst Mex Seguro Soc 47(6):651–658Google Scholar
  19. 19.
    Shayesta D, Chan KJ, Montaner JSG, Hogg RS (2006) Complementary and alternative medicine use in British Columbia -a survey of HIV positive people on antiretroviral therapy. Complement Ther Clin Pract 12:242–248Google Scholar
  20. 20.
    Tanaka E, Hisawa S (1999) Clinically significant pharmacokinetic drug interactions with psychoactive drugs: antidepressants and antipsychotics and the cytochrome P450 system. J Clin Pharmacy Ther 24:7–16Google Scholar
  21. 21.
    Indiana University School of Medicine. Cytochrome P450 Drug Interaction Table. Available at: Accessed 10 June 2010
  22. 22.
    Marchetti S, Mazzanti R, Beijnen JH, Schellens JH (2007) Concise review: clinical relevance of drug drug and herb drug interactions mediated by the ABC transporter ABCB1 (MDR1, P-glycoprotein). Oncologist 12:927–941PubMedGoogle Scholar
  23. 23.
    Garrovo C, Rosati A, Bartoli F, Decorti G (2006) St John’s wort modulation and developmental expression of multidrug transporters in the rat. Phytother Res 20:468–473PubMedGoogle Scholar
  24. 24.
    Harris RZ, Jang GR, Tsunoda S (2003) Dietary effects on drug metabolism and transport. Clin Pharmacokinet 42:1071–1088PubMedGoogle Scholar
  25. 25.
    Gurley BJ, Gardner SF, Hubbard MA et al (2002) Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 72:276–287PubMedGoogle Scholar
  26. 26.
    Gurley BJ, Swain A, Williams DK, Barone G, Battu SK (2008) Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: comparative effects of St. John’s wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics. Mol Nutr Food Res 52:772–779PubMedPubMedCentralGoogle Scholar
  27. 27.
    Wang LS, Zhou G, Zhu B (2004) St John’s wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole. Clin Pharmacol Ther 75:191–197PubMedGoogle Scholar
  28. 28.
    Jiang X, Williams KM, Liauw WS et al (2004) Effect of St. John’s wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 57:592–599PubMedPubMedCentralGoogle Scholar
  29. 29.
    Xu H, Liauw KM, Murray M, Day RO, McLachlan AJ (2008) Effects of St. John;s wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide. Br J Pharmacol 153:1579–1586PubMedPubMedCentralGoogle Scholar
  30. 30.
    Hafner V, Jäger M, Matthée A-K et al (2010) Effect of simultaneous induction and inhibition of CYP3A by St. John’s wort and ritonavir an CYP3A activity. Clin Pharmacol Ther 87:191–196PubMedGoogle Scholar
  31. 31.
    Markowitz JS, Devane CL, Chavin KD, Taylor RM, Ruan Y, Donovan JL (2003) Effects of garlic (Allium Sativum L.) supplementation on cytochrome P450 2D6 and 3A4 activity in healthy volunteers. Clin Pharmacol Ther 74:170–177PubMedGoogle Scholar
  32. 32.
    Gurley BJ, Gardner SF, Hubbard MA (2004) Vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus Aurantium, Echinacea Purpurea, milk thistle, and saw palmetto. Clin Pharmacol Ther 76:428–440PubMedGoogle Scholar
  33. 33.
    Gurley BJ, Barone GW, Williams DK (2006) Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin pharmacokinetics in humans. Drug Metab Dispos 34:69–74PubMedGoogle Scholar
  34. 34.
    Robertson SM, Davey RT, Voell J, Formentini E, Alfaro RM, Penzak SR (2008) Effect of Ginkgo biloba extract on lopinavir, midazolam, and fexofenadine pharmacokinetics in healthy subjects. Curr Med Res Opin 24:591–599PubMedGoogle Scholar
  35. 35.
    Jiang X, Williams KM, Liauw WS et al (2005) Effect of gingkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 59:425–432PubMedPubMedCentralGoogle Scholar
  36. 36.
    Mahutsky MA, Anderson GD, Miller JW, Elmer GW (2006) Ginkgo biloba: evaluation of CYP2C9 drug interactions in vitro and in vivo. Am J Ther 13:24–31Google Scholar
  37. 37.
    Yin OQP, Tomlinson B, Waye MMY, Chow AHL, Chow MSS (2004) Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole. Pharmacogenetics 14:841–850PubMedGoogle Scholar
  38. 38.
    Yasui-Furukori N, Furukori H, Kaneda A, Kaneko S, Tateishi T (2004) The effects of Ginkgo biloba extracts on the pharmacokinetics and pharmacodynamics of donepezil. J Clin Pharmacol 44:538–542PubMedGoogle Scholar
  39. 39.
    Penzak SR, Robertson SM, Hunt JD et al (2010) Echinacea Purpurea significantly induces cytochrome P450 3A (CYP3A) but does not alter lopinavir-ritonavir exposure in healthy subjects. Pharmacotherapy 30(8):797–805PubMedPubMedCentralGoogle Scholar
  40. 40.
    Gorski JC, Huang SM, Pinto A et al (2004) The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo. Clin Pharmacol Ther 75:89–100PubMedGoogle Scholar
  41. 41.
    Freeman C, Spelman K (2008) A critical evaluation of drug interactions with Echinacea spp. Mol Nutr Food Res 52:789–798PubMedGoogle Scholar
  42. 42.
    Jiang X, Blair EY, McLachlan AJ (2006) Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach. J Clin Pharmacol 46:1370–1378PubMedGoogle Scholar
  43. 43.
    Gurley BJ, Gardner SF, Hubbard MA et al (2005) 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 77:415–426PubMedPubMedCentralGoogle Scholar
  44. 44.
    Sandhu RS, Prescilla RP, Simonelli TM, Edwards DJ (2003) Influence of goldenseal root on the pharmacokinetics of indinavir. J Clin Pharmacol 43:1283–1288PubMedGoogle Scholar
  45. 45.
    Gurley BJ, Swain A, Barone GW et al (2007) Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans. Drug Metab Dispos 35:240–245PubMedGoogle Scholar
  46. 46.
    Donovan JL, DeVane CL, Chavin KD et al (2004) Multiple night-time doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers. Drug Metab Dispos 32:1333–1336PubMedGoogle Scholar
  47. 47.
    Dong SX, Ping ZZ, Xiao WZ et al (1999) Possible enhancement of the first-pass metabolism of phenacetin by ingestion of grape juice in Chinese subjects. Br J Clin Pharmacol 48:638–640Google Scholar
  48. 48.
    Donovan JL, Chavin KD, Devane CL et al (2004) Green tea (Camellia Sinensis) extract does not alter cytochrome p450 3A4 or 2D6 activity in healthy volunteers. Drug Metab Dispos 32:906–908PubMedGoogle Scholar
  49. 49.
    Tankanow R, Tamer HR, Streetman DS et al (2003) Interaction study between digoxin and a preparation of hawthorn (Crataegus Oxyacantha). J Clin Pharmacol 43:637–642PubMedGoogle Scholar
  50. 50.
    Markowitz JS, Donovan JL, Devane CL et al (2003) Multiple doses of saw palmetto (Serenoa repens) did not alter cytochrome P450 2D6 and 3A4 activity in normal volunteers. Clin Pharmacol Ther 74:536–542PubMedGoogle Scholar
  51. 51.
    Wang G, Xiao CQ, Li Z et al (2009) Effect of soy extract administration on losartan pharmacokinetics in healthy female volunteers. Ann Pharmacother 43:1045–1049PubMedGoogle Scholar
  52. 52.
    Anderson GD, Rosito G, Mohustsy MA, Elmer GW (2003) Drug interaction potential of soy extract and Panax ginseng. J Clin Pharmacol 43:643–648PubMedGoogle Scholar
  53. 53.
    Piscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J (2000) Indinavir concentrations and St. John’s wort. Lancet 355:547–548PubMedPubMedCentralGoogle Scholar
  54. 54.
    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 78:25–33PubMedGoogle Scholar
  55. 55.
    Piscitelli SC, Burstein AH, Welden N, Gallicano KD, Falloon J (2002) The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis 34:234–238PubMedGoogle Scholar
  56. 56.
    Gallicano K, Foster B, Choudhri S (2003) Effect of short-term administration of garlic supplements on single-dose ritonavir pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 55:199–202PubMedPubMedCentralGoogle Scholar
  57. 57.
    Piscitelli SC, Formentini E, Burstein AH, Alfaro R, Jagannatha S, Falloon J (2002) Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers. Pharmacotherapy 22:551–556PubMedGoogle Scholar
  58. 58.
    DiCenzo R, Shelton M, Jordan K et al (2003) Coadministration of milk thistle and indinavir in healthy subjects. Pharmacotherapy 23:866–870PubMedGoogle Scholar
  59. 59.
    Mills E, Wilson K, Clarke M (2005) Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis. Eur J Clin Pharmacol 61:1–7PubMedGoogle Scholar
  60. 60.
    Rajnarayana K, Reddy MS, Vidyasagar J, Krishna DR (2004) Study on the influence of silymarin pretreatment on metabolism and disposition of metronidazole. Arzneimittelforschung 54:109–113PubMedGoogle Scholar
  61. 61.
    Mogatle S, Skinner M, Mills E, Kanfer I (2008) Effect of African potato (Hypoxis hemerocallidea) on the pharmacokinetics of efavirenz. S Afr Med J 98:945–949PubMedGoogle Scholar
  62. 62.
    Cristiano C (2010) Herbal interactions on absorption of drugs: mechanisms of action and clinical risk assessment. Pharmacol Res 62:207–227Google Scholar
  63. 63.
    Jellin JM (2010) Natural medicines comprehensive database. Therapeutic Research Faculty, Stockton, CA. Available at Accessed 11 June 2010Google Scholar
  64. 64.
    Dürr D, Stieger B, Kullak-Ublick GA et al (2000) St. John’s wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 68:598–604PubMedGoogle Scholar
  65. 65.
    Staudinger JL, Ding X, Lichti K (2006) Pregnane X receptor and natural products: beyond drug-drug interactions. Expert Opin Drug Metab Toxicol 2:847–857PubMedPubMedCentralGoogle Scholar
  66. 66.
    de Maat MM, Hoetelmans RM, Math t RA et al (2001) Drug interaction between St John’s wort and nevirapine. AIDS 15:420–421PubMedGoogle Scholar
  67. 67.
    Hyland R, Jones BC, Smith DA (2003) Identification of the cytochrome P450 enzymes involved in the N-oxidation of voriconazole. Drug Metab Dispos 31:540–547PubMedGoogle Scholar
  68. 68.
    Moore LB, Goodwin B, Jones SA et al (2009) St. John’s wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci U S A 97:7500–7502Google Scholar
  69. 69.
    Zhou SF, Xue CC, XQ Y, Wang G (2007) Metabolic activation of herbal and dietary constituents and its clinical and toxicological implications: an update. Curr Drug Metab 8:526–553PubMedGoogle Scholar
  70. 70.
    Brady JF, Isizaki H, Fukuto JM et al (1991) Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolites. Chem Res Toxicol 4:642–647PubMedGoogle Scholar
  71. 71.
    Foster BC, Foster MS, Vandenhoek S (2001) An in vitro evaluation of human cytochrome P450 3A4 and P-glycoprotein inhibition by garlic. J Pharm Pharm Sci 4:176–184PubMedGoogle Scholar
  72. 72.
    Arnault I, Haffner T, Siess MH, Vollmar A, Kahane R, Auger J (2005) Analytical method for appreciation of garlic therapeutic potential and for validation of a new formulation. J Pharm Biomed Anal 37:963–970PubMedGoogle Scholar
  73. 73.
    Zou L, Harkey GL, Henderson GL (2002) Effects of herbal components on cDNA-expressed cytochrome P450 enzyme catalytic activity. Life Sci 71:1579–1589PubMedGoogle Scholar
  74. 74.
    Laroche M, Choudhri S, Gallicano K, Foster B (1998) Severe gastrointestinal toxicity with concomitant ingestion of ritonavir and garlic. Can J Infect Dis 9(Suppl A):471PGoogle Scholar
  75. 75.
    Budzinski JW, Trudeau VL, Drouin CE, Panahi M, Arnason JT, Foster BC (2007) Modulation of human cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in Caco-2 cell monolayers by selected commercial-source milk thistle and goldenseal products. Can J Physiol Pharmacol 85:966–978PubMedGoogle Scholar
  76. 76.
    Sridar C, Goosen TC, Kent UM, Williams JA, Hollenberg PF (2004) Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab Dispos 32:587–594PubMedGoogle Scholar
  77. 77.
    Molto J, Valle M, Miranda C, Cedeno S, Negredo E, Cloteta B (2012) Effect of milk thistle on the pharmacokinetics of Darunavir-ritonavir in HIV-infected patients. Antimicrob Agents Chemother 56(6):2837–2841PubMedPubMedCentralGoogle Scholar
  78. 78.
    Van Erp NP, Baker SD, Zhao M et al (2005) Effect of milk thistle (Silybum Marianum) on the pharmacokinetics of irinotecan. Clin Cancer Res 11:7800–7806PubMedGoogle Scholar
  79. 79.
    Sidelmann UG, Cornett C, Tjørnelund J, Hansen SHA (1996) Comparative study of precision cut liver slices, hepatocytes, and liver microsomes from the wistar rats using metronidazole as a model substrate. Xenobiotica 26:709–722PubMedGoogle Scholar
  80. 80.
    Beckmann-Knopp S, Rietbrock S, Weyhenmeyer R et al (2000) Inhibitory effects of silibinin on cytochrome P-450 enzymes in human liver microsomes. Pharmacol Toxicol 86:250–256PubMedGoogle Scholar
  81. 81.
    Kim DH, Jin YH, Park JB, Kobashi K (1994) Silymarin and its components are inhibitors of beta-glucuronidase. Biol Pharm Bull 17:443–445PubMedGoogle Scholar
  82. 82.
    Venkataramanan R, Ramachandran V, Komoroski BJ et al (2000) Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 28:1270–1273PubMedGoogle Scholar
  83. 83.
    Deng JW, Shon JH, Shin HJ et al (2008) Effect of silymarin supplement on the pharmacokinetics of rosuvastatin. Pharm Res 25:1807–1814PubMedGoogle Scholar
  84. 84.
    Blumenthal M (1998) The Complete German Commission E Monographs, Therapeutic Guide to Herbal Medicines. American Botanical Council, AustinGoogle Scholar
  85. 85.
    Kubota Y, Kobayashi K, Tanaka N et al (2003) Interaction of Ginkgo biloba extract (GBE) with hypotensive agent, nicardipine, in rats. In Vivo 17:409–412PubMedGoogle Scholar
  86. 86.
    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 70:2783–2792PubMedGoogle Scholar
  87. 87.
    Umegaki K, Saito K, Kubota Y, Sanada H, Yamada K, Shinozuka K (2002) Ginkgo biloba extract markedly induces pentoxyresorufin O-dealkylase activity in rats. Jpn J Pharmacol 90:345–351PubMedGoogle Scholar
  88. 88.
    Sugiyama T, Kubota Y, Shinozuka K, Yamada S, Yamada K, Umegaki K (2004) Induction and recovery of hepatic drug metabolizing enzymes in rats treated with Ginkgo biloba extract. Food Chem Toxicol 42:953–957PubMedGoogle Scholar
  89. 89.
    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 7:273–282PubMedGoogle Scholar
  90. 90.
    He N, Edeki TI (2003) Effects of ginseng and Ginkgo biloba components on CYP3A4 mediated testosterone 6beta-hydroxylation in human liver microsomes [abstract]. Clin Pharmacol Ther 73:50. Abstract PII-81Google Scholar
  91. 91.
    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(12):2006–2009PubMedGoogle Scholar
  92. 92.
    Morse GD, Rosenkranz S, Para MF et al (2005) Amprenavir and Efavirenz pharmacokinetics before and after the addition of nelfinavir, Indinavir, ritonavir, or Saquinavir in seronegative individuals. Antimicrob Agents Chemother 49:3373–3381PubMedPubMedCentralGoogle Scholar
  93. 93.
    Gallicano K, Khaliq Y, Carignan G, Tseng A, Walmsley S, Cameron DW (2001) A pharmacokinetic study of intermittent rifabutin dosing with a combination of ritonavir and saquinavir in patients infected with human immunodeficiency virus. Clin Pharmacol Ther 70:149–158PubMedGoogle Scholar
  94. 94.
    Wiegman DJ, Brinkman K, Franssen EJ (2009) Interaction of Ginkgo Biloba with efavirenz. AIDS 23:1184–1185PubMedGoogle Scholar
  95. 95.
    Kassahun K, McIntosh I, Cui D et al (2007) Metabolism and disposition in humans of Raltegravir (MK-0518), an anti-AIDS drug targeting the HIV-1 integrase enzyme. Drug Metab Dispos 35:1657–1663PubMedGoogle Scholar
  96. 96.
    Blonk M, Colbers A, Poirters A, Schouwenberg B, Burgera D (2012) Effect of Ginkgo biloba on the pharmacokinetics of Raltegravir in healthy volunteers. Antimicrob Agents Chemother 56(10):5070–5075PubMedPubMedCentralGoogle Scholar
  97. 97.
    Modarai M, Gertsch J, Suter A, Heinrich M, Kortenkamp A (2007) Cytochrome P450 inhibitory action of Echinacea preparations differs widely and co-varies with alkylamide content. J Pharm Pharmacol 59:567–573PubMedGoogle Scholar
  98. 98.
    The New Mexico AIDS Education and Training Center at the University of New Mexico Health Sciences Center. Echinacea. Fact Sheet Number 726. Available at: Accessed 11 June 2010
  99. 99.
    Al S, Laba JG, Moore JA, Lee TDG (2008) Echinacea-induced macrophage activation. Immunopharmacol Immunotoxicol 30:553–574Google Scholar
  100. 100.
    Morlat P, Pereira E, Clayette P et al (2008) Early evolution of plasma soluble TNF-alpha p75 receptor as a marker of progression in treated HIV-infected patients. AIDS Res Hum Retrovir 24:1383–1389PubMedGoogle Scholar
  101. 101.
    van den Bout-van den Beukel CJ, Koopmans PP, van der Ven AJ, De Smet PA, Burger DM (2006) Possible drug-metabolism interactions of medicinal herbs with antiretroviral agents. Drug Metab Rev 38:477–514PubMedGoogle Scholar
  102. 102.
    Kim M-G, Kim Y, Jeon J-Y, Kim D-S (2016) Effect of fermented red ginseng on cytochrome P450 and P-glycoprotein activity in healthy subjects, as evaluated using the cocktail approach. Br J Clin Pharmacol 82:1580–1590PubMedPubMedCentralGoogle Scholar
  103. 103.
    Streetman DS, Bertino JS, Nafziger AN (2000) Phenotyping of drug-metabolizing enzymes in adults: a review of in-vivo cytochrome P450 phenotyping probes. Pharmacogenetics 10(3):187–216PubMedPubMedCentralGoogle Scholar
  104. 104.
    Smith M, Lin KM, Zheng YP (2001) An open trial of nifedipine-herb interactions: nifedipine with St. John’s wort, ginseng, or ginkgo biloba [abstract]. Clin Pharmacol Ther 69:86. Abstract PIII-89Google Scholar
  105. 105.
    Henderson GL, Harkey MR, Gershwin ME, Hackman RM, Stern JS, Stresser DM (1999) Effects of ginseng components on c-DNA-expressed cytochrome P450 enzyme catalytic activity. Life Sci 65:209–214Google Scholar
  106. 106.
    Furutsu M, Koyama Y, Kusakabe M, Takahashi S (1997) Preventative effect of the extract of Du-zhong (Tochu) leaf and ginseng root on acute toxicity of chlorpyrifos. Jpn J Toxicol Environ Health 43:92–100Google Scholar
  107. 107.
    Malati CY, Robertson SM, Hunt JD et al (2012) Influence of Panax ginseng on cytochrome P450 (CYP)3A and P-glycoprotein (P-gp) activity in healthy participants. J Clin Pharmacol 52:932–939PubMedGoogle Scholar
  108. 108.
    Calderón MM, Chairez CL, Gordon LA, Alfaro RM, Kovacs JA, Penzak SR (2014) Influence of Panax ginseng on the steady state pharmacokinetic profile of lopinavir-ritonavir in healthy volunteers. Pharmacotherapy 34:1151PubMedPubMedCentralGoogle Scholar
  109. 109.
    Mills E, Cooper C, Seely D (2005) Kanfer. African herbal medicines in the treatment of HIV: Hypoxis and Sutherlandia. An overview of evidence and pharmacology. Nutr J 4:19PubMedPubMedCentralGoogle Scholar
  110. 110.
    Mills E, Foster BC, van Heeswijk R et al (2005) Impact of African herbal medicines on antiretroviral metabolism. AIDS 19:95–97PubMedGoogle Scholar
  111. 111.
    Nair VD, Foster BC, Thor Arnason J, Mills EJ, Kanfer I (2007) In vitro evaluation of human cytochrome P450 and P-glycoprotein-mediated metabolism of some phytochemicals in extracts and formulations of African potato. Phytomedicine 14:498–507PubMedGoogle Scholar
  112. 112.
    Brown L, Heyneke O, Brown D, van Wyk JP, Hamman JH (2008) Impact of traditional medicinal plant extracts on antiretroviral drug absorption. J Ethnopharmacol 119:588–592PubMedGoogle Scholar
  113. 113.
    Müller AC, Skinner MF, Kanfer I (2013) Effect of the African traditional medicine, Sutherlandia frutescens, on the bioavailability of the antiretroviral protease inhibitor, Atazanavir. Evid Based Complement Alternat Med 2013:324618PubMedPubMedCentralGoogle Scholar
  114. 114.
    US FDA (2016) Guidance for Industry Bioavailability and Bioequivalence Studies for Orally Administered Drug Products — General Considerations.Available at: Accessed on: 04 Nov 2016
  115. 115.
    Tsukamoto S, Aburatani M, Ohta T (2005) Isolation of CYP3A4 inhibitors from the Black Cohosh (Cimicifuga racemosa). Evid Based Complement Alternat Med 2:223–226PubMedPubMedCentralGoogle Scholar
  116. 116.
    Gurley BJ, Swain A, Hubbard MA et al (2008) 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 52:755–763PubMedPubMedCentralGoogle Scholar
  117. 117.
    Abourashed EA, Khan IA (2001) High-performance liquid chromatography determination of hydrastine and berberine in dietary supplements containing goldenseal. J Pharm Sci J Pharm Sci 90:817–822PubMedGoogle Scholar
  118. 118.
    Etheridge AS, Black SR, Patel PR, So J, Mathews JM (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 73:731–741PubMedGoogle Scholar
  119. 119.
    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 23:1553–1558PubMedGoogle Scholar
  120. 120.
    Lin HL, Liu TY, Lui WY, Chi CW (1999) Up-regulation of multidrug resistance transporter expression by berberine in human and murine hepatoma cells. Cancer 85(9):1937–1942PubMedGoogle Scholar
  121. 121.
    Mathews JM, Etheridge AS, Black SR (2002) Inhibition of human cytochrome P450 activities by kava extract and kavalactones. Drug Metab Dispos 30:1153–1157PubMedGoogle Scholar
  122. 122.
    Zou L, Henderson GL, Harkey MR, Sakai Y, Li A (2004) Effects of kava (Kava-kava, ’Awa, Yaqona, Piper methysticum) on c-DNA-expressed cytochrome P450 enzymes and human cryopreserved hepatocytes. Phytomedicine 11:285–294PubMedGoogle Scholar
  123. 123.
    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 18:2273–2281PubMedGoogle Scholar
  124. 124.
    Weiss J, Sauer A, Frank A, Unger M (2005) Extracts and kavalactones of Piper methysticum G. Forst (kava-kava) inhibit P-glycoprotein in vitro. Drug Metab Dispos 33:1580–1583PubMedGoogle Scholar
  125. 125.
    Escher M, Desmeules J, Giostra E, Mentha G (2001) Drug points: hepatitis associated with kava, a herbal remedy for anxiety. BMJ 322:139PubMedPubMedCentralGoogle Scholar
  126. 126.
    Russmann S, Lauterberg BH, Hebling A (2001) Kava Hepatotoxicity [letter]. Ann Intern Med 135:68PubMedGoogle Scholar
  127. 127.
    Liver Toxicity with kava (2001) Pharmacist’s letter/Prescriber’s letter. Ann Intern Med 18(1):180115Google Scholar
  128. 128.
    Consultation letter MLX 286: Proposals to prohibit the herbal ingredient Kava-Kava (Piper methysticum) in unlicensed medicines. Medicines Control Agency, United Kingdom, July 19, 2002Google Scholar
  129. 129.
    Li XZ, Ramzan I (2010) Role of ethanol in kava hepatotoxicity. Phytother Res 24:475–480PubMedGoogle Scholar
  130. 130.
    Lefebvre T, Foster BC, Drouin CE et al (2004) In vitro activity of commercial valerian root extracts against human cytochrome P450 3A4. J Pharm Pharmaceut Sci 7:265–273Google Scholar
  131. 131.
    Hellum BH, Nilsen OG (2008) In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products. Basic Clin Pharmacol Toxicol 102:466–475PubMedGoogle Scholar
  132. 132.
    Sustiva Prescribing Information (2010) Bristol Myers Squibb Pharma. Sustiva Prescribing Information, PrincetonGoogle Scholar
  133. 133.
    Chantre P, Cappelaere A, Leblan D et al (2000) Efficacy and tolerance or Harpagophytum procumbens versus diacerhein in treatment of osteoarthritis. Phytomedicine 7:177–184PubMedGoogle Scholar
  134. 134.
    Chisholm A, Mann J, Skeaff M et al (1998) A diet rich in walnuts favourably influences plasma fatty acid profile in moderately hyperlipidaemic subjects. Eur J Clin Nutr 52:12–16PubMedGoogle Scholar
  135. 135.
    Freedman JE, Parker C, Li L et al (2001) Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation 103:2792–2798PubMedGoogle Scholar
  136. 136.
    Nuttall SL, Kendall MJ, Bombardelli E, Morazzoni P (1998) An evaluation of the antioxidant activity of a standardized grape seed extract, Leucoselect. J Clin Pharm Ther 23:385–389PubMedGoogle Scholar
  137. 137.
    Nishikawa M, Ariyoshi N, Kotani A et al (2004) Effects of continuous ingestion of green tea or grape seed extracts on the pharmacokinetics of midazolam. Drug Metab Pharmacokinet 19:280–289PubMedGoogle Scholar
  138. 138.
    Raucy JL (2003) Regulation of CYP3A4 expression in human hepatocytes by pharmaceuticals and natural products. Drug Metab Dispos 31:533–539PubMedGoogle Scholar
  139. 139.
    Sohn OS, Surace A, Fiala ES et al (1994) Effects of green and black tea on hepatic xenobiotic metabolizing systems in the male F344 rat. Xenobiotica 24:119–127PubMedGoogle Scholar
  140. 140.
    Bonkovsky HL (2006) Hepatotoxicity associated with supplements containing Chinese green tea (Camellia sinensis). Ann Intern Med 144:68–71PubMedGoogle Scholar
  141. 141.
    Jimenez-Saenz M, Martinez-Sanchez MDC (2006) Acute hepatitis associated with the use of green tea infusions. J Hepatol 44:616–619PubMedGoogle Scholar
  142. 142.
    Suekawa M, Ishige A, Yuasa K et al (1984) Pharmacological studies on ginger. I. Pharmacological actions of pungent constitutents, (6)-gingerol and (6)-shogaol. J Pharmacobiodyn 7:836–848PubMedGoogle Scholar
  143. 143.
    Pongrojpaw D, Somprasit C, Chanthasenanont A (2007) A randomized comparison of ginger and dimenhydrinate in the treatment of nausea and vomiting in pregnancy. J Med Assoc Thail 90:1703–1709Google Scholar
  144. 144.
    Langner E, Greifenberg S, Gruenwald J (1998) Ginger: history and use. Adv Ther 15:25–44PubMedGoogle Scholar
  145. 145.
    Castro AF, Altenberg GA (1997) Inhibition of drug transport by genistein in multidrug-resistant cells expressing P-glycoprotein. Biochem Pharmacol 53:89–93PubMedGoogle Scholar
  146. 146.
    Jäger W, Zembsch B, Wolschann P et al (1998) Metabolism of the anticancer drug flavopiridol, a new inhibitor of cyclin dependent kinases, in rat liver. Life Sci 62:1861–1873PubMedGoogle Scholar
  147. 147.
    South African Development Committee. Ministerial consultative meeting on nutrition and HIV/AIDS, Johannesburg, South Africa, January 20, 2002Google Scholar
  148. 148.
    Morito K, Hirose T, Kinjo J et al (2001) Interaction of phytoestrogens with estrogen receptors alpha and beta. Biol Pharm Bull 24:351–356PubMedGoogle Scholar
  149. 149.
    Halm BM, Franke AA, Ashburn LA, Hebshi SM, Wilkens LR (2008) Oral antibiotics decrease urinary isoflavonoid excretion in children after soy consumption. Nutr Cancer 60:14–22PubMedGoogle Scholar
  150. 150.
    Kleijnen J (1994) Evening primrose oil. BMJ 309:824–825PubMedPubMedCentralGoogle Scholar
  151. 151.
    Belch J, Hill A (2000) Evening primrose oil and borage oil in rheumatologic conditions. Am J Clin Nutr 71:352S–356SPubMedGoogle Scholar
  152. 152.
    Gurley BJ, Gardner SF, Hubbard MA (2000) Content versus label claims in ephedra-containing dietary supplements. Am J Health-Syst Pharm 57:963–969PubMedGoogle Scholar
  153. 153.
    Parasrampuria J, Schwartz K (1998) Quality control of dehydroepiandrosterone dietary supplement products. JAMA 280:1565. [Letter]PubMedGoogle Scholar
  154. 154.
    Liberti LE, Der Marderosian A (1978) Evaluation of commercial ginseng products. J Pharm Sci 67:1487–1489PubMedGoogle Scholar
  155. 155.
    Cui J, Garle M, Eneroth P, Björkhem I (1994) What do commercial ginseng preparations contain? Lancet 344:134. [Letter]PubMedGoogle Scholar
  156. 156.
    Heptinstall S, Awang DV, Dawson BA, Kindack D, Knight DW, May J (1992) Parthenolide content and bioactivity of feverfew (Tanacetum parthenium (L.) Schulkz-Bip). Estimation of commercial and authenticated feverfew products. J Pharm Pharmacol 44:391–395PubMedGoogle Scholar
  157. 157.
    Webb G (1997) “fX” chemically adulterated product does not contain kava. HerbalGram 39:9Google Scholar
  158. 158.
    Saper RB, Phillips RS, Sehgal A et al (2008) Lead, mercury, and arsenic in US- and Indian-manufactured Ayurvedic medicines sold via the internet. JAMA 300:915–923PubMedPubMedCentralGoogle Scholar
  159. 159.
    Corns CM (2003) Herbal remedies and clinical biochemistry. Ann Clin Biochem 40(Pt 5):489–507PubMedGoogle Scholar
  160. 160.
    Obach RS (2000) 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 294:88–95PubMedGoogle Scholar
  161. 161.
    Kashuba ADM, Bertino JS Jr (2005) Mechanisms of drug interactions I: absorption, metabolism and excretion. In: Piscitelli SC, Rodvold KA (eds) Drug interactions in infectious diseases, 2nd edn. Human Press, Totowa, pp 13–39Google Scholar
  162. 162.
    Weber K, Schneider M, Sacks H et al (2002) Trends in complementary/alternative medicine (CAM) use in a large cohort of HIV-infected women in the US from 1994–2001. XIV International AIDS Conference, Barcelona Spain. 7–12 July 2002: Abstract WePeB6004Google Scholar
  163. 163.
    Behm Dillon DM, Penzak SR, Bailey Klepser T (2004) The use of herbals by patients with HIV. Adv Pharm 2:41–60Google Scholar
  164. 164.
    Lorenc A, Robinson N (2013) A review of the use of complementary and alternative medicine and HIV: issues for patient care. AIDS Patient Care STDs 27(9):503–510PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Pharmacy PracticeMCOPS, Manipal UniversityManipalIndia
  2. 2.Department of PharmacotherapyUniversity of North Texas System College of PharmacyFort WorthUSA

Personalised recommendations