Assessing Transporter-Mediated Natural Product-Drug Interactions via In vitro-In vivo Extrapolation: Clinical Evaluation with a Probe Cocktail.

Assessing Transporter-Mediated Natural Product-Drug Interactions via In vitro-In vivo Extrapolation: Clinical Evaluation with a Probe Cocktail. Clin Pharmacol Ther. 2020 Nov 11;: Authors: Nguyen JT, Tian DD, Tanna RS, Hadi DL, Bansal S, Calamia JC, Arian CM, Shireman LM, Molnár B, Horváth M, Kellogg JJ, Layton ME, White JR, Cech NB, Boyce RD, Unadkat JD, Thummel KE, Paine MF Abstract The botanical natural product goldenseal can precipitate clinical drug interactions by inhibiting cytochrome P450 (CYP) 3A and CYP2D6. Besides P-glycoprotein, effects of goldenseal on other clinically relevant transporters remain unknown. Established transporter-expressing cell systems were used to determine the inhibitory effects of a goldenseal extract, standardized to the major alkaloid berberine, on transporter activity. Using recommended basic models, the extract was predicted to inhibit the efflux transporter breast cancer resistance protein (BCRP) and uptake transporters organic anion transporting polypeptide (OATP) 1B1/3. Using a cocktail approach, effects of the goldenseal product on BCRP, OATP1B1/3, organic anion transporters (OATs), organic cation transporters (OCTs), multidrug and toxin extrusion (MATE) proteins, and CYP3A were next evaluated in 16 healthy volunteers. As expected, goldenseal increased the area under the plasma concentration-time curve (AUC0-inf ) of midazolam (CYP3A; positive control), with a geometric mean ratio (GMR) [90%...
Source: Clinical Pharmacology and Therapeutics - Category: Drugs & Pharmacology Authors: Tags: Clin Pharmacol Ther Source Type: research