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Planta Med 2004; 70(9): 784-791
DOI: 10.1055/s-2004-827223
Review
© Georg Thieme Verlag KG Stuttgart · New York

Pharmacokinetic Herb-Drug Interactions: Are Preventive Screenings Necessary and Appropriate?

Veronika Butterweck1 , Hartmut Derendorf1 , Wilhelm Gaus2 , Adolf Nahrstedt3 , Volker Schulz4 , Matthias Unger5
  • 1Department of Pharmaceutics, University of Florida, Gainesville, FL, USA
  • 2Abteilung Biometrie und Medizinische Dokumentation, Ulm, Germany
  • 3Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany
  • 4Berlin, Germany
  • 5Institut für Pharmazie, Würzburg, Germany
Weitere Informationen

Publikationsverlauf

Received: June 14, 2004

Accepted: July 12, 2004

Publikationsdatum:
23. September 2004 (online)

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Abstract

Pharmacokinetic interactions often occur as a result of activity changes of drug-metabolizing and transporting proteins, especially cytochrome P450 (CYP) isoenzymes and P-glycoprotein (P-gp). The activity of these enzymes and drug transporters can be enhanced or inhibited by synthetic drugs as well as by natural products. Since the number of herb-drug interactions has increased in recent years, systematic in vitro screenings and more clinical studies to identify such interactions were proposed for herbal medicinal products. However, previous results regarding this issue are not only contradictory but also of less predictability. One reason for the discrepancies could be the lack of validation of the recommended in vitro tests. Furthermore, it has to be considered that pharmacokinetic drug interactions are not only mediated by herbal medicines but also by several foods, beverages and life-style products. Since herbal medicines are considered to have a broad therapeutic range, a preventive risk assessment for pharmacokinetic drug interactions should first be realized for synthetic drugs with a narrow therapeutic index. Efforts to identify all possible interactions will lead to limitless investigations and to inconsistent decisions.

Key words

Pharmacokinetic drug interactions - cytochrome P450 - P-glycoprotein - herb-drug interactions - food-drug interactions - preventive screenings

References

  • 1 Hammerness P, Basch E, Ulbricht C, Barrette E P, Foppa I, Basch S, Bent S, Boon H, Ernst E. St John's wort: a systematic review of adverse effects and drug interactions for the consultation psychiatrist.  Psychosomatics. 2003;  44 271-82
    CrossrefPubMedGoogle Scholar
  • 2 Henderson L, Yue Q Y, Bergquist C, Gerden B, Arlett P. St John’s wort (Hypericum perforatum): drug interactions and clinical outcomes.  Br J Clin Pharmacol. 2002;  54 349-56
    CrossrefPubMedGoogle Scholar
  • 3 Schulz V, Johne A. Side effects and drug interactions. In: Müller WE, ed St. John's Wort and its active principles in depression and anxiety. Milestones in Drug Therapy. Basel, Switzerland; Birkhäuser 2004
    Google Scholar
  • 4 Ernst E. Possible interactions between synthetic and herbal medicinal products. Part 1: a systematic review of the indirect evidence.  Perfusion. 2000;  13 4-15
    PubMedGoogle Scholar
  • 5 Izzo A A, Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review.  Drugs. 2001;  61 2163-75
    CrossrefPubMedGoogle Scholar
  • 6 Boon H, Jurgens T. Drug Interactions with Natural Health Products: A Discussion Paper. Health Canada Website 2002
    Google Scholar
  • 7 Hohl K, Gaus W. Bibliography on interactions between drugs and herbs and between drugs and food-supplements. 2004 http://www.uni-ulm.de/uni/fak/medizin/biodok/v4/herb_drug_interactions.html
    Google Scholar
  • 8 Donato M T, Castell J V. Strategies and molecular probes to investigate the role of cytochrome P450 in drug metabolism: focus on in vitro studies.  Clin Pharmacokinet. 2003;  42 153-78
    PubMedGoogle Scholar
  • 9 Limon L. Drug interactions. Decreasing the risk. American Pharmaceutical Association Annual Meeting Washington, DC; 2000
    Google Scholar
  • 10 Wacher V J, Wu C Y, Benet L Z. Overlapping substrate and tissue distribution of cytochrome P450 and P-glycoprotein: implications for drug delivery and activity in cancer chemotherapy.  Mol Carcinogen. 1995;  13 129-34
    PubMedGoogle Scholar
  • 11 Gatmaitan Z C, Arias I M. Structure and function of P-glycoprotein in normal liver and small intestine.  Adv Pharmacol. 1993;  24 77-97
    PubMedGoogle Scholar
  • 12 Lown K S, Mayo R R, Leichtman A B, Hsiao H L, Turgeon D K, Schmiedlin-Ren P, Brown M B, Guo W, Rossi S J, Benet L Z, Watkins P B. Role of intestinal P-glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclosporine.  Clin Pharmacol Ther. 1997;  62 246-80
    PubMedGoogle Scholar
  • 13 Paine M F, Khalighi M, Fisher J M, Shen D D, Kunze K L, Marsh C L, Perkins J D, Thummel K E. Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism.  J Pharmacol Exp Ther. 1997;  283 1552-62
    PubMedGoogle Scholar
  • 14 Harris R Z, Jang G R, Tsunoda S. Dietary effects on drug metabolism and transport.  Clin Pharmacokinet. 2003;  42 1071-88
    CrossrefPubMedGoogle Scholar
  • 15 Kivisto K T, Lilja J J, Backman J T, Neuvonen P J. Repeated consumption of grapefruit juice considerably increases plasma concentrations of cisapride.  Clin Pharmacol Ther. 1999;  66 448-53
    PubMedGoogle Scholar
  • 16 Estabrook R W. A passion for P450 s (remembrances of the early history of research on cytochrome P450).  Drug Metab Dispos. 2003;  31 1461-73
    CrossrefPubMedGoogle Scholar
  • 17 Sorensen J M. Herb-drug, food-drug, nutrient-drug, and drug-drug interactions: mechanisms involved and their medical implications.  J Altern Complement Med. 2002;  8 293-308
    CrossrefPubMedGoogle Scholar
  • 18 Foster B C, Vandenhoek S, Hana J, Krantis A, Akhtar M H, Bryan M, Budzinski J W, Ramputh A, Arnason J T. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products.  Phytomedicine. 2003;  10 334-42
    CrossrefPubMedGoogle Scholar
  • 19 Strandell J, Neil A, Carlin G. An approach to the in vitro evaluation of potential for cytochrome P450 enzyme inhibition from herbals and other natural remedies.  Phytomedicine. 2004;  11 98-104
    CrossrefPubMedGoogle Scholar
  • 20 Lampen A. Interaktion zwischen Metabolismus und Transport von toxisch relevanten Substanzen in der gastrointestinalen Barriere.  Biospektrum. 2004;  10 157-9
    PubMedGoogle Scholar
  • 21 Tsunoda S M, Harris R Z, Christians U, Velez R L, Freeman R B, Benet L Z, Warshaw A. Red wine decreases cyclosporine bioavailability.  Clin Pharmacol Ther. 2001;  70 462-7
    PubMedGoogle Scholar
  • 22 Unger M. Wie Naturstoffe die Bioverfuegbarkeit von Arzneistoffen beeinflussen.  Pharm Ztg. 2004;  149 979-86
    PubMedGoogle Scholar
  • 23 U.S. Food Administration A. Guidance for industry: Drug metabolism/Drug interaction studies in the drug development process: Studies in vitro . Rockville, MD; 1997 http://www.fda.gov/cber/cberftp.html
    Google Scholar
  • 24 Gorski J C, Huang S M, Pinto A, Hamman M A, Hilligoss J K, Zaheer N A, Desai M, Miller M, Hall S D. The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo .  Clin Pharmacol Ther. 2004;  75 89-100
    CrossrefPubMedGoogle Scholar
  • 25 Piscitelli S C, Burstein A H, Welden N, Gallicano K D, Falloon J. The effect of garlic supplements on the pharmacokinetics of saquinavir.  Clin Infect Dis. 2002;  34 234-8
    CrossrefPubMedGoogle Scholar
  • 26 Zou L, Harkey M R, Henderson G L. Effects of intrinsic fluorescence and quenching on fluorescence-based screening of natural products.  Phytomedicine. 2002;  9 263-7
    PubMedGoogle Scholar
  • 27 Bapiro T E, Egnell A C, Hasler J A, Masimirembwa C M. Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s.  Drug Metab Dispos. 2001;  29 30-5
    PubMedGoogle Scholar
  • 28 Budzinski J W, Foster B C, Vandenhoek S, Arnason J T. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures.  Phytomedicine. 2000;  7 273-82
    CrossrefPubMedGoogle Scholar
  • 29 Obach R S. 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
    PubMedGoogle Scholar
  • 30 BfArM. Bewertung möglicher pharmakokinetischer Arzneimittel-Interaktionen mit Phytopharmaka (Entwurf). 2004 www.bfarm.de/de/Arzneimittel/bes_therap/am_pflanzl/int_20 040 116.pdf
    Google Scholar
  • 31 Chang W H, Augustin B, Lane H Y, ZumBrunnen T, Liu H C, Kazmi Y, Jann M W. In-vitro and in-vivo evaluation of the drug-drug interaction between fluvoxamine and clozapine.  Psychopharmacology (Berl). 1999;  145 91-8
    CrossrefPubMedGoogle Scholar
  • 32 Zuber R, Anzenbacherova E, Anzenbacher P. Cytochromes P450 and experimental models of drug metabolism.  J Cell Mol Med. 2002;  6 189-98
    PubMedGoogle Scholar
  • 33 Derendorf H, Hochhaus G. Handbook of Pharmacokinetic-Pharmacodynamic Correlations. Boca Raton, Florida; 1995: 483
    Google Scholar
  • 34 Derendorf H, Meibohm B. Modeling of pharmacokinetic/pharmacodynamic (PK/PD) relationships: concenpts and perspectives.  Pharm Res. 1999;  16 176-85
    CrossrefPubMedGoogle Scholar
  • 35 Bjornsson T D, Callaghan J T, Einolf H J, Fischer V, Gan L, Grimm S, Kao J, King S P, Miwa G, Ni L, Kumar G, McLeod J, Obach S R, Roberts S, Roe A, Shah A, Snikeris F, Sullivan J T, Tweedie D, Vega J M, Walsh J, Wrighton S A. The conduct of in vitro and in vivo drug-drug interaction studies: a PhRMA perspective.  J Clin Pharmacol. 2003;  43 443-69
    CrossrefPubMedGoogle Scholar
  • 36 Huang S M. Issues and challenges in the evaluation and labeling of drug interaction potentials of NME FDA Clinical Pharmacology Subcommittee Advisory Board Meeting. Washington DC; 2003
    Google Scholar
  • 37 Freeman B D, Zehnbauer B A, McGrath S, Borecki I, Buchman T G. Cytochrome P450 polymorphisms are associated with reduced warfarin dose.  Surgery. 2000;  128 281-5
    CrossrefPubMedGoogle Scholar
  • 38 Prior T I, Chue P S, Tibbo P, Baker G B. Drug metabolism and atypical antipsychotics.  Eur Neuropsychopharmacol. 1999;  9 301-9
    PubMedGoogle Scholar
  • 39 Peng C C, Glassman P A, Trilli L E, Hayes-Hunter J, Good C B. Incidence and severity of potential drug-dietary supplement interactions in primary care patients: an exploratory study of 2 outpatient practices.  Arch Intern Med. 2004;  164 630-6
    CrossrefPubMedGoogle Scholar
  • 40 Harder S, Thurmann P. Clinically important drug interactions with anticoagulants. An update.  Clin Pharmacokinet. 1996;  30 416-44
    PubMedGoogle Scholar
  • 41 Vistisen K, Loft S, Poulsen H E. Cytochrome P450 1A2 activity in man measured by caffeine metabolism: effect of smoking, broccoli and exercise.  Adv Exp Med Biol. 1991;  283 407-11
    PubMedGoogle Scholar
  • 42 Lampe J W, King I B, Li S, Grate M T, Barale K V, Chen C, Feng Z, Potter J D. Brassica vegetables increase and apiaceous vegetables decrease cytochrome P450 1A2 activity in humans: changes in caffeine metabolite ratios in response to controlled vegetable diets.  Carcinogenesis. 2000;  21 1157-62
    CrossrefPubMedGoogle Scholar
  • 43 Jeppesen U, Loft S, Poulsen H E, Brsen K. A fluvoxamine-caffeine interaction study.  Pharmacogenetics. 1996;  6 213-22
    CrossrefPubMedGoogle Scholar
  • 44 Monks T J, Caldwell J, Smith R L. Influence of methylxanthine-containing foods on theophylline metabolism and kinetics.  Clin Pharmacol Ther. 1979;  26 513-24
    PubMedGoogle Scholar
  • 45 Cone E J, Fant R V, Henningfield J E. Nicotine and Tobacco. In: Mozayani A, Raymon LP, eds Handbook of Drug Interactions. Totova, New Jersey; Humana Press 2004: 463-92
    Google Scholar
  • 46 Bailey D G, Spence J D, Munoz C, Arnold J MO. Interaction of citrus juices with felodipine and nifedipine.  Lancet. 1991;  337 268-9
    CrossrefPubMedGoogle Scholar
  • 47 Bailey D G, Malcolm A O, Munoz C, Spence J D. Grapefruit juice and naringin on nisoldipine pharmacokinetics.  Clin Pharmacol Ther. 1993;  54 589-94
    PubMedGoogle Scholar
  • 48 Soons P A, Vogels B A, Roosenmalen M C, Shoemaker H C, Uchida E, Edgar B, Lundahl J, Cohen A F, Bremer D D. Grapefruit juice and cimetidine inhibit stereoselective metabolism of nitrendipine in humans.  Clin Pharmacol Ther. 1991;  50 393-403
    PubMedGoogle Scholar
  • 49 Ducharme M P, Provenzano R, Dehoorne-Smith M, Edwards D J. Trough concentration of cyclosporine in blood following administration with grapefruit juice.  Br J Clin Pharmacol. 1993;  36 457-9
    PubMedGoogle Scholar
  • 50 Westveer M K, Farquhar M L, George P, Mayers J T. Co-administration of grapefruit juice increases tacrolimus levels in liver transplant recipients.  Ann Meet Am Soc Transplant Physicians. 1996;  202 115
    PubMedGoogle Scholar
  • 51 Kupferschmidt H HT, Ha H R, Ziegler W H, Meier P J, Krahenbuhl S. Interaction between grapefruit juice and midazolam in human.  Clin Pharmacol Ther. 1995;  58 20-8
    CrossrefPubMedGoogle Scholar
  • 52 Hukkinen S K, Varhe A, Olkkola K T, Neuvonen P J. Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice.  Clin Pharmacol Ther. 1995;  58 127-31
    CrossrefPubMedGoogle Scholar
  • 53 Benton R E, Honig P K, Zamani K, Cantilena L R, Woosley R L. Grapefruit juice alters terfenadine pharmacokinetics, resulting in prolongation of repolarization on the electrocardiogram.  Clin Pharmacol Ther. 1996;  59 383-8
    CrossrefPubMedGoogle Scholar
  • 54 Ozdemir M, Atkan Y, Boydag B S, Cibgi M I, Musmul A. Interaction between grapefruit jucie and diazepam in human.  Eur J Drug Metab Pharmacokin. 1998;  23 55-9
    PubMedGoogle Scholar
  • 55 Kupferschmidt H HT, Fattinger K E, Ha H R, Follath F, Krahenbuhl S. Grapefruit juice enhances the bioavailability of the HIV protease inhibitor saquinavir in man.  Br J Clin Pharmacol. 1998;  45 355-9
    PubMedGoogle Scholar
  • 56 Weber A, Jager R, Borner A, Klinger G, Vollanth R, Matth K. Can grapefruit juice influence ethinylestradiol bioavailability.  Contraception. 1996;  53 41-7
    CrossrefPubMedGoogle Scholar
  • 57 Fuhr U, Klittch K, Atab A H. Inhibitory effect of grapefruit juice and its bitter principle, naringenin, on CYP1A2 dependent metabolism of caffeine in man.  Br J Clin Pharmacol. 1993;  35 431-6
    PubMedGoogle Scholar
  • 58 Simopoulos A P, Kifer R R, Martin R E. Health effects of polyunsaturated fatty acids in seafoods. Orlando, San Diego, New York; Academic Press Inc 1986: 383-401
    Google Scholar
  • 59 Conney A H, Pantuck E J, Hsiao K C, Garland W A, Anderson K E, Alvares A P, Kappas A. Enhanced phenacetin metabolism in human subjects fed charcoal-broiled beef.  Clin Pharmacol Ther. 1976;  20 633-42
    PubMedGoogle Scholar
  • 60 Pantuck E J, Pantuck C B, Garland W A, Min B H, Wattenberg L W, Anderson K E, Kappas A, Conney A H. Stimulatory effect of Brussels sprouts and cabbage on human drug metabolism.  Clin Pharmacol Ther. 1979;  25 88-95
    PubMedGoogle Scholar
  • 61 Pantuck E J, Pantuck C B, Anderson K E, Wattenberg L W, Conney A H, Kappas A. Effect of Brussels sprouts and cabbage on drug conjugation.  Clin Pharmacol Ther. 1984;  35 161-9
    PubMedGoogle Scholar
  • 62 Pantuck E J, Pantuck C B, Anderson K E, Conney A H, Kappas A. Cigarette smoking and chlorpromazine disposition and actions.  Clin Pharmacol Ther. 1982;  31 533-8
    CrossrefPubMedGoogle Scholar
  • 63 Bailey D G, Arnold J M, Munoz C, Spence J D. Grapefruit juice-felodipine interaction: mechanism, predictability, and effect of naringin.  Clin Pharmacol Ther. 1993;  53 637-42
    PubMedGoogle Scholar
  • 64 Bailey D G, Kreeft J H, Munoz C, Freeman D J, Bend J R. Grapefruit juice-felodipine interaction: effect of naringin and 6′,7′-dihydroxybergamottin in humans.  Clin Pharmacol Ther. 1998;  64 248-56
    CrossrefPubMedGoogle Scholar
  • 65 Girre C, Lucas D, Hispard E, Menez C, Dally S, Menez J F. Assessment of cytochrome P4502E1 induction in alcoholic patients by chlorzoxazone pharmacokinetics.  Biochem Pharmacol. 1994;  47 1503-8
    CrossrefPubMedGoogle Scholar
  • 66 Kall M A, Vang O, Clausen J. Effects of dietary broccoli on human in vivo drug metabolizing enzymes: evaluation of caffeine, oestrone and chlorzoxazone metabolism.  Carcinogenesis. 1996;  17 793-9
    PubMedGoogle Scholar
  • 67 Leclercq I, Desager J P, Horsmans Y. Inhibition of chlorzoxazone metabolism, a clinical probe for CYP2E1, by a single ingestion of watercress.  Clin Pharmacol Ther. 1998;  64 144-9
    CrossrefPubMedGoogle Scholar
  • 68 Malhotra S, Bailey D G, Paine M F, Watkins P B. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins.  Clin Pharmacol Ther. 2001;  69 14-23
    CrossrefPubMedGoogle Scholar

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