title: Established HPLC fraction analysis to predict furanocoumarin-based herb-drug metabolic interactions.
abstract: An attempt was made in this study to predict the potential for metabolic interactions of herbal extracts of drugs from their chromatographic profiles in reverse-phase high-performance liquid chromatography (RP-HPLC). Twenty-nine structurally related furanocoumarin compounds with known inhibitory interactions with cytochrome P450 3A (CYP3A), which is important for phase-I drug metabolism, were selected as a model system. A sigmoidal relationship was established between the CYP3A inhibitory potency (y) and the RP-HPLC total peak response unit (R(u), x) as y = 85.36 x (14.86 + x)⁻¹ with a correlation coefficient of 0.63. The sigmoidal curve could be divided into three ranges designated low, medium and high risk that were used to indicate the relative inhibitory potency of the metabolic interactions of herbs or traditional Chinese herb medicines with CYP3A. These predictive classifications provide information or might be useful for 'risk category' decisions concerning herb-drug interactions.
authors.affiliation: College of Pharmacy, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.
authors.forename: Ming-Thau
authors.initials: MT
authors.lastname: Sheu
authors.forename: Ying-Ku
authors.initials: YK
authors.lastname: Lin
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Huang
authors.forename: Hsiu-O
authors.initials: HO
authors.lastname: Ho
mesh_terms: D000818:Animals; D019661:Apiaceae / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000378:metabolism; D011564:Furocoumarins / Q000032:analysis / Q000378:metabolism*; D041743:Herb-Drug Interactions; D020128:Inhibitory Concentration 50; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D009543:Nifedipine / Q000737:chemistry / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D004365:Drugs, Chinese Herbal; D011564:Furocoumarins; D051544:Cytochrome P-450 CYP3A; D009543:Nifedipine