Artitaya Thiengsusuk1,2, Kanyarat Boonprasert1, Kesara Na-Bangchang3,4. 1. Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Klong Luang, Pathum Thani, 12120, Thailand. 2. Drug Discovery and Development Center, Office of Advanced Science and Technology, Thammasat University, Bangkok, Thailand. 3. Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Klong Luang, Pathum Thani, 12120, Thailand. kesaratmu@yahoo.com. 4. Drug Discovery and Development Center, Office of Advanced Science and Technology, Thammasat University, Bangkok, Thailand. kesaratmu@yahoo.com.
Abstract
BACKGROUND AND OBJECTIVES: Hepatic drug metabolism is a key influence on the efficacy and safety of medicines from both chemical and natural product sources. Studies of the metabolism of synthetic compounds, herbal medicines/supplements, and herb-derived bioactive compounds are therefore challenging. The aim of the present review is to provide a summary of the approaches/techniques that are currently being employed to investigate different aspects of the metabolism of herbs and herb-derived compounds (reaction phenotyping, metabolite profiling, metabolic clearance prediction, metabolic/pharmacokinetic drug interactions, and metabolism-related pharmacokinetic studies), including their limitations. METHODS: A thorough search of the PubMed database was performed using the terms 'Cancer' AND 'Cytochrome P450 (CYP)' OR 'Phase I metabolism' OR 'Phase II metabolism' AND 'Natural product' OR 'Herbal medicine' OR 'Herbal product' OR 'Herb-derived compound.' RESULTS: Most of the studies (84 studies, 83.2%) retrieved during the search investigated metabolic/pharmacokinetic drug interactions. Three (3.0%), 7 (6.9%), 6 (5.9%), and 1 (1.0%) study involved metabolism-related pharmacokinetic studies, reaction phenotyping, metabolite profiling, and prediction of metabolic clearance, respectively. CONCLUSIONS: Various studies reported conflicting results, with the results depending on the nature of the herb investigated (extracts or active constituents) and the biochemical tool (subcellular fractions, cells, or recombinant enzymes) and study system (in vitro/in vivo/ex vivo/clinical) applied. Each approach/system has its own advantages and disadvantages. Selecting the most appropriate approaches/systems allows us to extract the most meaningful and clinically relevant information on the metabolic pathways (the metabolites generated and the enzymes involved) and the potential drug interactions of herb-derived compounds for cancer therapy and prevention. Human primary hepatocytes are the best model that can be applied in any metabolic study. Human liver microsomes (HLMs) are a useful biochemical tool for preliminary drug metabolism studies. Recombinant microsomes that express specific enzymes and CYP-isoform-specific monoclonal antibodies are useful tools for enzyme inhibition studies.
BACKGROUND AND OBJECTIVES: Hepatic drug metabolism is a key influence on the efficacy and safety of medicines from both chemical and natural product sources. Studies of the metabolism of synthetic compounds, herbal medicines/supplements, and herb-derived bioactive compounds are therefore challenging. The aim of the present review is to provide a summary of the approaches/techniques that are currently being employed to investigate different aspects of the metabolism of herbs and herb-derived compounds (reaction phenotyping, metabolite profiling, metabolic clearance prediction, metabolic/pharmacokinetic drug interactions, and metabolism-related pharmacokinetic studies), including their limitations. METHODS: A thorough search of the PubMed database was performed using the terms 'Cancer' AND 'Cytochrome P450 (CYP)' OR 'Phase I metabolism' OR 'Phase II metabolism' AND 'Natural product' OR 'Herbal medicine' OR 'Herbal product' OR 'Herb-derived compound.' RESULTS: Most of the studies (84 studies, 83.2%) retrieved during the search investigated metabolic/pharmacokinetic drug interactions. Three (3.0%), 7 (6.9%), 6 (5.9%), and 1 (1.0%) study involved metabolism-related pharmacokinetic studies, reaction phenotyping, metabolite profiling, and prediction of metabolic clearance, respectively. CONCLUSIONS: Various studies reported conflicting results, with the results depending on the nature of the herb investigated (extracts or active constituents) and the biochemical tool (subcellular fractions, cells, or recombinant enzymes) and study system (in vitro/in vivo/ex vivo/clinical) applied. Each approach/system has its own advantages and disadvantages. Selecting the most appropriate approaches/systems allows us to extract the most meaningful and clinically relevant information on the metabolic pathways (the metabolites generated and the enzymes involved) and the potential drug interactions of herb-derived compounds for cancer therapy and prevention. Human primary hepatocytes are the best model that can be applied in any metabolic study. Human liver microsomes (HLMs) are a useful biochemical tool for preliminary drug metabolism studies. Recombinant microsomes that express specific enzymes and CYP-isoform-specific monoclonal antibodies are useful tools for enzyme inhibition studies.
Authors: David J Greenblatt; Lisa L von Moltke; Yan Luo; Elke S Perloff; Kelly A Horan; Allison Bruce; Robyn C Reynolds; Jerold S Harmatz; Bharathi Avula; Ikhlas A Khan; Peter Goldman Journal: J Clin Pharmacol Date: 2006-02 Impact factor: 3.126
Authors: D Dürr; B Stieger; G A Kullak-Ublick; K M Rentsch; H C Steinert; P J Meier; K Fattinger Journal: Clin Pharmacol Ther Date: 2000-12 Impact factor: 6.875
Authors: J Christopher Gorski; Shiew-Mei Huang; Amar Pinto; Mitchell A Hamman; Janna K Hilligoss; Narjis A Zaheer; Mehul Desai; Margaret Miller; Stephen D Hall Journal: Clin Pharmacol Ther Date: 2004-01 Impact factor: 6.875