Tags

Type your tag names separated by a space and hit enter

Rhinacanthin-C Mediated Herb-Drug Interactions with Drug Transporters and Phase I Drug-Metabolizing Enzymes.
Drug Metab Dispos. 2019 10; 47(10):1040-1049.DM

Abstract

Rhinacanthin-C is a major active constituent in Rhinacanthus nasutus (L.) Kurz, a plant widely used in herbal remedies. Its potential for pharmacokinetic herb-drug interaction may exist with drug transporters and drug metabolizing enzymes. This study assessed the possibility for rhinacanthin-C-mediated drug interaction by determining its inhibitory effects against major human efflux and influx drug transporters as well as various human cytochrome P450(CYP) isoforms. Rhinacanthin-C demonstrated a moderate permeability through the Caco-2 monolayers [Papp (AP-to-BL) = 1.26 × 10-6 cm/s]. It significantly inhibited transport mediated by both P-glycoprotein (P-gp) (IC50 = 5.20 µM) and breast cancer resistance protein (BCRP) (IC50 = 0.83 µM) across Caco-2 and BCRP-overexpressing Madin-Darby canine kidney II cells (MDCKII) cells. This compound also strongly inhibited uptake mediated by organic anion-transporting polypeptide 1B1 (OATP1B1) (IC50 = 0.70 µM) and OATP1B3 (IC50 = 3.95 µM) in OATP1B-overexpressing HEK cells. In addition to its inhibitory effect on these drug transporters, rhinacanthin-C significantly inhibited multiple human CYP isoforms including CYP2C8 (IC50 = 4.56 µM), 2C9 (IC50 = 1.52 µM), 2C19 (IC50 = 28.40 µM), and 3A4/5 (IC50 = 53 µM for midazolam and IC50 = 81.20 µM for testosterone), but not CYP1A2, 2A6, 2B6, 2D6, and 2E1. These results strongly support a high propensity for rhinacanthin-C as a perpetrator of clinical herb-drug interaction via inhibiting various influx and efflux drug transporters (i.e., P-gp, BCRP, OATP1B1, and OATP1B3) and CYP isoforms (i.e., CYP2C8, CYP2C9, and CYP2C19). Thus, the potential for significant pharmacokinetic herb-drug interaction should be addressed when herbal products containing rhinacanthin-C are to be used in conjunction with other prescription drugs.

Authors+Show Affiliations

Departments of Pharmacology and Physiology (W.D., S.J.) and Pharmaceutics and Industrial Pharmacy (N.V.), Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand; and National Cancer Institute, Bangkok, Thailand (P.S.).Departments of Pharmacology and Physiology (W.D., S.J.) and Pharmaceutics and Industrial Pharmacy (N.V.), Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand; and National Cancer Institute, Bangkok, Thailand (P.S.).Departments of Pharmacology and Physiology (W.D., S.J.) and Pharmaceutics and Industrial Pharmacy (N.V.), Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand; and National Cancer Institute, Bangkok, Thailand (P.S.).Departments of Pharmacology and Physiology (W.D., S.J.) and Pharmaceutics and Industrial Pharmacy (N.V.), Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand; and National Cancer Institute, Bangkok, Thailand (P.S.) suree.j@pharm.chula.ac.th.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31399508

Citation

Dunkoksung, Wilasinee, et al. "Rhinacanthin-C Mediated Herb-Drug Interactions With Drug Transporters and Phase I Drug-Metabolizing Enzymes." Drug Metabolism and Disposition: the Biological Fate of Chemicals, vol. 47, no. 10, 2019, pp. 1040-1049.
Dunkoksung W, Vardhanabhuti N, Siripong P, et al. Rhinacanthin-C Mediated Herb-Drug Interactions with Drug Transporters and Phase I Drug-Metabolizing Enzymes. Drug Metab Dispos. 2019;47(10):1040-1049.
Dunkoksung, W., Vardhanabhuti, N., Siripong, P., & Jianmongkol, S. (2019). Rhinacanthin-C Mediated Herb-Drug Interactions with Drug Transporters and Phase I Drug-Metabolizing Enzymes. Drug Metabolism and Disposition: the Biological Fate of Chemicals, 47(10), 1040-1049. https://doi.org/10.1124/dmd.118.085647
Dunkoksung W, et al. Rhinacanthin-C Mediated Herb-Drug Interactions With Drug Transporters and Phase I Drug-Metabolizing Enzymes. Drug Metab Dispos. 2019;47(10):1040-1049. PubMed PMID: 31399508.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rhinacanthin-C Mediated Herb-Drug Interactions with Drug Transporters and Phase I Drug-Metabolizing Enzymes. AU - Dunkoksung,Wilasinee, AU - Vardhanabhuti,Nontima, AU - Siripong,Pongpun, AU - Jianmongkol,Suree, Y1 - 2019/08/09/ PY - 2018/11/26/received PY - 2019/07/15/accepted PY - 2019/8/11/pubmed PY - 2020/6/2/medline PY - 2019/8/11/entrez SP - 1040 EP - 1049 JF - Drug metabolism and disposition: the biological fate of chemicals JO - Drug Metab. Dispos. VL - 47 IS - 10 N2 - Rhinacanthin-C is a major active constituent in Rhinacanthus nasutus (L.) Kurz, a plant widely used in herbal remedies. Its potential for pharmacokinetic herb-drug interaction may exist with drug transporters and drug metabolizing enzymes. This study assessed the possibility for rhinacanthin-C-mediated drug interaction by determining its inhibitory effects against major human efflux and influx drug transporters as well as various human cytochrome P450(CYP) isoforms. Rhinacanthin-C demonstrated a moderate permeability through the Caco-2 monolayers [Papp (AP-to-BL) = 1.26 × 10-6 cm/s]. It significantly inhibited transport mediated by both P-glycoprotein (P-gp) (IC50 = 5.20 µM) and breast cancer resistance protein (BCRP) (IC50 = 0.83 µM) across Caco-2 and BCRP-overexpressing Madin-Darby canine kidney II cells (MDCKII) cells. This compound also strongly inhibited uptake mediated by organic anion-transporting polypeptide 1B1 (OATP1B1) (IC50 = 0.70 µM) and OATP1B3 (IC50 = 3.95 µM) in OATP1B-overexpressing HEK cells. In addition to its inhibitory effect on these drug transporters, rhinacanthin-C significantly inhibited multiple human CYP isoforms including CYP2C8 (IC50 = 4.56 µM), 2C9 (IC50 = 1.52 µM), 2C19 (IC50 = 28.40 µM), and 3A4/5 (IC50 = 53 µM for midazolam and IC50 = 81.20 µM for testosterone), but not CYP1A2, 2A6, 2B6, 2D6, and 2E1. These results strongly support a high propensity for rhinacanthin-C as a perpetrator of clinical herb-drug interaction via inhibiting various influx and efflux drug transporters (i.e., P-gp, BCRP, OATP1B1, and OATP1B3) and CYP isoforms (i.e., CYP2C8, CYP2C9, and CYP2C19). Thus, the potential for significant pharmacokinetic herb-drug interaction should be addressed when herbal products containing rhinacanthin-C are to be used in conjunction with other prescription drugs. SN - 1521-009X UR - https://www.unboundmedicine.com/medline/citation/31399508/Rhinacanthin_C_Mediated_Herb_Drug_Interactions_with_Drug_Transporters_and_Phase_I_Drug_Metabolizing_Enzymes_ DB - PRIME DP - Unbound Medicine ER -