CLINICALLY SIGNIFICANT PHARMACOKINETIC DRUG-HERBAL DIETARY SUPPLEMENTS INTERACTIONS


CLINICALLY SIGNIFICANT PHARMACOKINETIC DRUG-HERBAL DIETARY SUPPLEMENTS INTERACTIONS

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Title: CLINICALLY SIGNIFICANT PHARMACOKINETIC DRUG-HERBAL DIETARY SUPPLEMENTS INTERACTIONS
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Article_Title: CLINICALLY SIGNIFICANT PHARMACOKINETIC DRUG-HERBAL DIETARY SUPPLEMENTS INTERACTIONS
Authors: Simona Conea1, Neli K. Olah2, Claudiu Morgovan3, Claudia C. Toma4, Adriana Dărăban5
Affiliation: 1Department of Clinical Pharmacy, Faculty of Medicine and Pharmacy, “Vasile Goldiş” Western University Arad,
2Department of Pharmaceutical Industry, Faculty of Medicine and Pharmacy, “Vasile Goldiş” Western University Arad.
3Department of Pharmaceutical Management and Marketing, Faculty of Medicine and Pharmacy, “Vasile Goldiş” Western University Arad.
4Department of Pharmacognosy, Faculty of Medicine and Pharmacy, “Vasile Goldiş” Western University Arad.
5Department of Inorganic Chemistry, Faculty of Medicine and Pharmacy, “Vasile Goldiş” Western University Arad.
Abstract: Most commercially available botanical supplements exhibit considerable variability in phytochemical profiles, and label claims for “standardized” marker compounds can deviate considerably from actual content. Such variations can have significant influence on results of clinical studies evaluating dietary supplements efficacy or its herb-drug interaction risk.
There are also plant extracts that can influence the drug disposition or can act as inhibitors or inductors of CYP isoforms.
In summary, dosage forms containing standardized herbal extracts, when administered at per label recommended doses, do not pose a risk for clinically relevant herb-drug interactions. However, daily doses exceeding these doses or prolonged treatment may increase prospects for interactions.
Keywords: pharmacokinetic, herb-drug interaction, dietary supplements, metabolic enzymes, transporter activity.
References: Basch E, Ulbricht C, Basch S, Dalton S, Ernst E, Foppa I, Szapary P, Tiffany N, Orlando CW, Vora M, An evidence-based systematic review of Echinacea (E. angustifolia DC, E. pallida, E. purpurea) by the Natural Standard Research Collaboration, J Herb Pharmacother, 5, 57–88, 2005.
Chan PC, Xia Q, Fu PP, Ginkgo biloba leaves extract: biological, medicinal and toxicological effects. J Environ Sci Health C, 25, 211–244, 2007.
Chen C, Choiu W, Zhang J. Comparison of the pharmacological effects of Panax ginseng and Panax quinquefolium. Acta Pharmacol Sin., 29, 1103–1108, 2008.
Fisher CD, Augustine LM, Maher JM, Nelson DM, Slitt AL, Klaassen CD, Lehman-McKeeman LD, Cherrington NJ. Induction of drug metabolizing enzymes by garlic and allyl sulfide compounds via activation of constitutive androstane receptor and nuclear factor E2-related factor, Drug Metab Dispos 35: 995–1000, 2007.
Gorski JC, Huang SM, Mitchell AP, Hamman A, Hilligoss JK, Zaheer NA, Desai M, Miller M, Hall SD, The effect of echinacea (Echinacea purpurea) on cytochrome P450 activity in vivo, Clin Pharmacol Ther., 75, 89–100, 2004.
Greenblatt DJ, Leigh-Pemberton RA, von Moltke LL. In vitro interactions of water-soluble garlic components with human cytochromes P450, J Nutr., 136, 806–809, 2006.
Gurley BJ, Barone GW, Williams DK, Carrier J, Breen P, Yates CR, Song P, Hubbard MA, Tong Y, Cheboyina S, Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin pharmacokinetics in humans, Drug Metab Dispos., 34, 69–74, 2006.
Gurley BJ, Fifer EK, Gardner Z, Pharmacokinetic Herb-Drug Interactions (Part 2). Planta Med, 78, 1490–1514, 2012.
Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Khan IA, Shah A. 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, 2005.
Gurley BJ, Swain A, Hubbard MA, Williams DK, Barone G, Hartsfield F, Tong Y, Carrier DJ, Cheboyina S, Battu SK, 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, 2008.
Han Y, Guo D, Chen Y, Chen Y, Tan Z‑R, Zhou H, Effect of silymarin on the pharmacokinetics of losartan and its active metabolite E-3174 in healthy Chinese volunteers. Eur J Clin Pharmacol., 65, 585–591, 2009.
Hawke RL, Schrieber SJ, Soule TA, Wen Z, Smith PC, Reddy R, Wahed AS, Silymarin ascending multiple oral dosing phase I study in noncirrhotic patients with chronic hepatitis C. J Clin Pharmacol, 50, 434–449, 2010.
Huang Y, Jiang B, Nuntanakorn P, Kennelly EJ, Shord S, Lawal TO, Soni KK, Mahady GB, Fukinolic acid derivatives and triterpene glycosides from black cohosh inhibit CYP isozymes, but are not cytotoxic to Hep-G2 cells in vitro, Curr Drug Saf, 5, 118–124, 2010.
Hypericum Depression Trial Study Group, Effect of Hypericum perforatum (St John`s wort) in major depressive disorder: a randomized controlled trial. JAMA 14, 1807–1814, 2002.
Iwata H, Tezuka Y, Kadota S, Hiratuska A, Watabe T. Identification and characterization of potent CYP3A4 inhibitors in Schisandra fruit extract. Drug Metab Dispos, 32, 1351–1358, 2004.
Janetzky K, Morreale AP, Probable interaction between warfarin and ginseng. Am J Health Syst Pharm, 54, 692–693, 1997.
Loizou GD, Crocker J, The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazone, Hum Exp Toxicol., 20, 321–327, 2001.
Miguez M-P, Anundi I, Sainz-Pardo LA, Lindros KO, Hepatoprotective mechanism of silymarin: no evidence for involvement of cytochrome P450 2E1. Chem Biol Interact, 91, 51–63, 1994.
Mueller SC, Uehleke B, Woehling H, Petzsch M, Majcher-Peszynska J, Hehl EM, Sievers H, Frank B, Riethling AK, Drewelow B. Effect of St John`s wort dose and preparations on the pharmacokinetics of digoxin. Clin Pharmacol Ther., 75, 546–557, 2004.
Murray M, Mechanisms of inhibitory and regulatory effects of methylenedioxyphenyl compounds on cytochrome P450-dependent drug oxidation. Curr Drug Metab, 1, 67–84, 2000.
Penzak SR, Robertson SM, Hunt JD, Chairez C, Malati CY, Alfaro RM, Stevenson JM, Kovacs JA, Echinacea purpurea significantly induces cytochrome P450 3A activity but does not alter lopinavir-ritonavir exposure in healthy subjects, Pharmacotherapy, 30, 797–805, 2010.
Shams T, Setia MS, Hemmings R, McCusker J, Sewitch M, Ciampi A, Efficacy of black cohosh-containing preparations on menopausal symptoms a meta analysis. Altern Health Med, 16, 36–44, 2010.
Toselli F, Matthias A, Gillam EMJ, Echinacea metabolism and drug interactions: the case for standardization of a complementary medicine, Life Sci, 85, 97–106, 2009.
Tsukamoto S, Aburatani M, Ohta T, Isolation of CYP3A4 inhibitors from the black cohosh (Cimicifuga racemosa). eCAM, 2, 223–226, 2005.
Ulbricht C, Basch E, Boon H, Ernst E, Hammerness P, Sollars D, Tsourounis C. Safety review of kava (Piper methysticum) by the Natural Standard Research Collaboration. Expert Opin Drug Saf, 4, 779–794, 2005.
Read_full_article: pdf/vol15/iss1-4/10 JMA 2012 Suciu.pdf
Correspondence: Conea Simona, Department of Clinical Pharmacy, Faculty of Medicine and Pharmacy, Western University Arad, Tel. 0745709995, e-mail: suciu_simona@yahoo.com.

Read full article
Article Title: CLINICALLY SIGNIFICANT PHARMACOKINETIC DRUG-HERBAL DIETARY SUPPLEMENTS INTERACTIONS
Authors: Simona Conea1, Neli K. Olah2, Claudiu Morgovan3, Claudia C. Toma4, Adriana Dărăban5
Affiliation: 1Department of Clinical Pharmacy, Faculty of Medicine and Pharmacy, “Vasile Goldiş” Western University Arad,
2Department of Pharmaceutical Industry, Faculty of Medicine and Pharmacy, “Vasile Goldiş” Western University Arad.
3Department of Pharmaceutical Management and Marketing, Faculty of Medicine and Pharmacy, “Vasile Goldiş” Western University Arad.
4Department of Pharmacognosy, Faculty of Medicine and Pharmacy, “Vasile Goldiş” Western University Arad.
5Department of Inorganic Chemistry, Faculty of Medicine and Pharmacy, “Vasile Goldiş” Western University Arad.
Abstract: Most commercially available botanical supplements exhibit considerable variability in phytochemical profiles, and label claims for “standardized” marker compounds can deviate considerably from actual content. Such variations can have significant influence on results of clinical studies evaluating dietary supplements efficacy or its herb-drug interaction risk.
There are also plant extracts that can influence the drug disposition or can act as inhibitors or inductors of CYP isoforms.
In summary, dosage forms containing standardized herbal extracts, when administered at per label recommended doses, do not pose a risk for clinically relevant herb-drug interactions. However, daily doses exceeding these doses or prolonged treatment may increase prospects for interactions.
Keywords: pharmacokinetic, herb-drug interaction, dietary supplements, metabolic enzymes, transporter activity.
References: Basch E, Ulbricht C, Basch S, Dalton S, Ernst E, Foppa I, Szapary P, Tiffany N, Orlando CW, Vora M, An evidence-based systematic review of Echinacea (E. angustifolia DC, E. pallida, E. purpurea) by the Natural Standard Research Collaboration, J Herb Pharmacother, 5, 57–88, 2005.
Chan PC, Xia Q, Fu PP, Ginkgo biloba leaves extract: biological, medicinal and toxicological effects. J Environ Sci Health C, 25, 211–244, 2007.
Chen C, Choiu W, Zhang J. Comparison of the pharmacological effects of Panax ginseng and Panax quinquefolium. Acta Pharmacol Sin., 29, 1103–1108, 2008.
Fisher CD, Augustine LM, Maher JM, Nelson DM, Slitt AL, Klaassen CD, Lehman-McKeeman LD, Cherrington NJ. Induction of drug metabolizing enzymes by garlic and allyl sulfide compounds via activation of constitutive androstane receptor and nuclear factor E2-related factor, Drug Metab Dispos 35: 995–1000, 2007.
Gorski JC, Huang SM, Mitchell AP, Hamman A, Hilligoss JK, Zaheer NA, Desai M, Miller M, Hall SD, The effect of echinacea (Echinacea purpurea) on cytochrome P450 activity in vivo, Clin Pharmacol Ther., 75, 89–100, 2004.
Greenblatt DJ, Leigh-Pemberton RA, von Moltke LL. In vitro interactions of water-soluble garlic components with human cytochromes P450, J Nutr., 136, 806–809, 2006.
Gurley BJ, Barone GW, Williams DK, Carrier J, Breen P, Yates CR, Song P, Hubbard MA, Tong Y, Cheboyina S, Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin pharmacokinetics in humans, Drug Metab Dispos., 34, 69–74, 2006.
Gurley BJ, Fifer EK, Gardner Z, Pharmacokinetic Herb-Drug Interactions (Part 2). Planta Med, 78, 1490–1514, 2012.
Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Khan IA, Shah A. 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, 2005.
Gurley BJ, Swain A, Hubbard MA, Williams DK, Barone G, Hartsfield F, Tong Y, Carrier DJ, Cheboyina S, Battu SK, 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, 2008.
Han Y, Guo D, Chen Y, Chen Y, Tan Z‑R, Zhou H, Effect of silymarin on the pharmacokinetics of losartan and its active metabolite E-3174 in healthy Chinese volunteers. Eur J Clin Pharmacol., 65, 585–591, 2009.
Hawke RL, Schrieber SJ, Soule TA, Wen Z, Smith PC, Reddy R, Wahed AS, Silymarin ascending multiple oral dosing phase I study in noncirrhotic patients with chronic hepatitis C. J Clin Pharmacol, 50, 434–449, 2010.
Huang Y, Jiang B, Nuntanakorn P, Kennelly EJ, Shord S, Lawal TO, Soni KK, Mahady GB, Fukinolic acid derivatives and triterpene glycosides from black cohosh inhibit CYP isozymes, but are not cytotoxic to Hep-G2 cells in vitro, Curr Drug Saf, 5, 118–124, 2010.
Hypericum Depression Trial Study Group, Effect of Hypericum perforatum (St John`s wort) in major depressive disorder: a randomized controlled trial. JAMA 14, 1807–1814, 2002.
Iwata H, Tezuka Y, Kadota S, Hiratuska A, Watabe T. Identification and characterization of potent CYP3A4 inhibitors in Schisandra fruit extract. Drug Metab Dispos, 32, 1351–1358, 2004.
Janetzky K, Morreale AP, Probable interaction between warfarin and ginseng. Am J Health Syst Pharm, 54, 692–693, 1997.
Loizou GD, Crocker J, The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazone, Hum Exp Toxicol., 20, 321–327, 2001.
Miguez M-P, Anundi I, Sainz-Pardo LA, Lindros KO, Hepatoprotective mechanism of silymarin: no evidence for involvement of cytochrome P450 2E1. Chem Biol Interact, 91, 51–63, 1994.
Mueller SC, Uehleke B, Woehling H, Petzsch M, Majcher-Peszynska J, Hehl EM, Sievers H, Frank B, Riethling AK, Drewelow B. Effect of St John`s wort dose and preparations on the pharmacokinetics of digoxin. Clin Pharmacol Ther., 75, 546–557, 2004.
Murray M, Mechanisms of inhibitory and regulatory effects of methylenedioxyphenyl compounds on cytochrome P450-dependent drug oxidation. Curr Drug Metab, 1, 67–84, 2000.
Penzak SR, Robertson SM, Hunt JD, Chairez C, Malati CY, Alfaro RM, Stevenson JM, Kovacs JA, Echinacea purpurea significantly induces cytochrome P450 3A activity but does not alter lopinavir-ritonavir exposure in healthy subjects, Pharmacotherapy, 30, 797–805, 2010.
Shams T, Setia MS, Hemmings R, McCusker J, Sewitch M, Ciampi A, Efficacy of black cohosh-containing preparations on menopausal symptoms a meta analysis. Altern Health Med, 16, 36–44, 2010.
Toselli F, Matthias A, Gillam EMJ, Echinacea metabolism and drug interactions: the case for standardization of a complementary medicine, Life Sci, 85, 97–106, 2009.
Tsukamoto S, Aburatani M, Ohta T, Isolation of CYP3A4 inhibitors from the black cohosh (Cimicifuga racemosa). eCAM, 2, 223–226, 2005.
Ulbricht C, Basch E, Boon H, Ernst E, Hammerness P, Sollars D, Tsourounis C. Safety review of kava (Piper methysticum) by the Natural Standard Research Collaboration. Expert Opin Drug Saf, 4, 779–794, 2005.
*Correspondence: Conea Simona, Department of Clinical Pharmacy, Faculty of Medicine and Pharmacy, Western University Arad, Tel. 0745709995, e-mail: suciu_simona@yahoo.com.