Herbal Extracts used for Upper Respiratory Tract Infections: Are there Clinically Relevant Interactions with the Cytochrome P450 Enzyme System?

Abstract

The regulatory requirements for assessing potential interactions between herbal medicinal products and other medicines can cause specific, additional phytopharmaceutical problems. In this short review we assess the state of our knowledge for herbal extracts commonly used as over the counter (OTC) products for upper respiratory infections and which in many cases are considered to have immunomodulatory effects. Overall, the data on the safety of these products is still limited and only in the case of Echinacea preparations can preliminary conclusions be drawn. The available evidence points to weak cytochrome P450 inhibition which is unlikely to be of clinical relevance.

Abbreviations

CYP:cytochrome P450

HMP(s):herbal medicinal product(s)

OTC:over the counter (drugs)

Key words

Upper respiratory infections - cytochrome P450 - drug safety - herb-drug interactions - Echinacea - Kan Jang (Andrographis paniculata/Eleutherococcus senticosus) - Asteraceae

References

• 1 BfArM. Bewertung möglicher pharmakokinetischer Arzneimittel-Interaktionen mit Phytopharmaka. 2004. Available at http://www.bfarm.de/cln_042/nn_424 630/DE/Arzneimittel/besTherap/amPflanz/ampflanz-node.html. Accessed August 20, 2006. 
• 2 Williamson E M. Interactions between herbal and conventional medicines.  Expert Opin Drug Saf. 2005;  4 1-24
• 3 Van den Bout-van den Beukel C JP, Koopmans P P, van der Ven A JAM, De Smet P AGM, Burger D M. Possible rrug - metabolism interactions of medicinal herbs with antiretroviral agents.  Drug Metabol Rev. 2006;  38 477-514
• 4 Barnes J, Anderson L A, Gibbons S, Phillipson J D. Echinacea angustifolia (D.C.) Hell. Echinacea pallida (Nutt.) Nutt., Echinacea purpurea (L.) Moench: a review of their chemistry, pharmacology and clinical properties.  J Pharm Pharmacol. 2005;  57 929-54
• 5 Woelkart K, Marth E, Suter A, Schoop R, Raggam R B, Koidl C. et al . Bioavailability and pharmacokinetics of Echinacea purpurea preparations and their interactions with the immune system.  Int J Clin Pharmacol Ther. 2006;  44 401-8
• 6 Shah S A, Sander S, White C M, Rinaldi M, Coleman C I. Evaluation of Echinacea for the prevention and treatment of the common cold: a meta-analysis.  Lancet Infect Dis. 2007;  7 473-80
• 7 Schoop R, Klein P, Suter A, Johnson S L. Echinacea in the prevention of induced rhinovirus colds: A meta-analysis.  Clin Ther. 2006;  28 174-83
• 8 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
• 9 Yale S H. Glurich I. Analysis of the inhibitory potential of Gingko biloba, Echinacea purpurea, and Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9.  J Altern Complement Med. 2005;  11 433-9
• 10 Gorski J C, Huang S M, Pinto A, Hamman M A, Hilligoss J K, Zaheer N A. et al . The effect of Echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo.  Clin Pharmacol Ther. 2004;  75 9-100
• 11 Gurley B J, Gardner S F, Hubbard M A, Williams D K, Gentry W B, Carrier J. et al . In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle and saw palmetto.  Clin Pharmacol Ther. 2004;  76 428-40
• 12 Modarai M, Gertsch J, Suter A, Heinrich M, Kortenkamp A. Cytochrome P450 inhibitory action of Echinacea preparations differs widely and co-varies with alkylamide content.  J Pharm Pharmacol. 2007;  59 567-73
• 13 Matthias A, Gillam E M, Penman K G, Matovic N J, Bone K M, De Voss J J. et al . Cytochrome P450 enzyme-mediated degradation of Echinacea alkylamides in human liver microsomes.  Chem Biol Interact. 2005;  155 62-70
• 14 Hellum B H, Hu Z, Nilsen O G. The induction of CYP1A2, CYP2D6 and CYP3A4 by six trade herbal products in cultured primary human hepatocytes.  Basic Clin Pharmacol Toxicol. 2007;  100 3-30
• 15 Hovhannisyan A S, Abrahamyan H, Gabrielyan E S, Panossian A G. The effect of Kan Jang extract on the pharmacokinetics and pharmacodynamis of warfarin in rats.  Phytomedicine. 2006;  13 318-23
• 16 Pekthong D, Martin H, Abadie C, Bonet A, Heyd B. Differential inhibition of rat and human hepatic cytochrome P450 by Andrographis paniculata extract and andrographolide. J Ethnopharmacol, advance online publication; doi: 10.1016/j.jep.2007.10.013
• 17 Jarukamjorn K, Don-in K, Makejaruskul C, Laha T, Daodee S, Pearaksa P. et al . Impact of Andrographis paniculata crude extract on mouse hepatic cytochrome P450 enzymes.  J Ethnopharmacol. 2006;  105 464-7
• 18 Donovan J L, DeVane C L, Chavin K D, Taylor R M, Mardowitz J S. Siberian ginseng (Eleutherococcus senticosus) effects on CYP2D6 and CYP3A4 activity in normal volunteers.  Drug Metab Dispos. 2003;  31 519-22