Predicting In Vivo Caffeine/ Angelica dahurica and Caffeine/ Salvia miltiorrhiza Pharmacokinetic Interactions in Humans with In Vitro CYP1A2 Inhibition Data
Year: 2014
Type: article
Abstract: Currently, no existing models allow for holistic predictions of drug-herb interactions.To investigate possible interactions between drugs and current use 'traditional' medicines, extracts of Angelica dahurica and Salvia miltiorrhiza were examined in vitro and in vivo for their ability to modify human caffeine metabolism.Consumption of either herbal decoction by volunteers significantly elevated caffeine retention (>200%).Human liver microsomes were treated in vitro with candidate precipitants identified in each herb in addition to ethanolic extracts of the whole herb(s).All treatments reversibly inhibited CYP1A2-mediated caffeine metabolism; Ki values of pure precipitants ranged from 0.28 -2.55 µM.IC50 values for A. dahurica and S. miltiorrhiza extracts were 1.15e-3 and 1.6e-3 mg/L respectively.Human pharmacokinetic values were estimated for each precipitant and used with in vitro PK data to conservatively predict caffeine retention.This study allows for prediction of hepatic threshold precipitant concentrations associated with clinically relevant inhibition of CYP450 function.
Source: Summit (Simon Fraser University)
Author: Mohamed Mishal Sheriffdeen
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W8352280