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The potential of Sutherlandia frutescens for herb-drug interaction.
Drug Metab Dispos. 2013 Feb; 41(2):488-97.DM

Abstract

In Africa, Sutherlandia frutescens is a popular medicinal herb widely consumed by people living with human immunodeficiency virus/AIDS. Concomitant use with antiretroviral drugs has generated concerns of herb-drug interaction (HDI). This study investigated the inhibitory effects of the crude extracts of S. frutescens on the major cytochrome P450 isozymes with the use of pooled human liver microsomes. Its effect on the metabolic clearance of midazolam using cryopreserved hepatocytes was also monitored. The potential of S. frutescens to inhibit human ATP-binding cassette transporters (P-gp and BCRP) and the human organic anion transporting polypeptide (OATP1B1 and OATP1B3) activity was assessed using cell lines overexpressing the transporter proteins. S. frutescens showed inhibitory potency for CYP1A2 (IC(50) = 41.0 µg/ml), CYP2A6 (IC(50) = 160 µg/ml), CYP2B6 (IC(50) = 20.0 µg/ml), CYP2C8 (IC(50) = 22.4 µg/ml), CYP2C9 (IC(50) = 23.0 µg/ml), CYP2C19 (IC(50) = 35.9 µg/ml), and CYP3A4/5 (IC(50) = 17.5 µg/ml [with midazolam1'-hydroxylation]; IC(50) = 28.3 µg/ml [with testosterone 6β-hydroxylation]). Time-dependent (irreversible) inhibition by S. frutescens was observed for CYP3A4/5 (K(I) = 296 µg/ml, k(inact) = 0.063 min(-1)) under the conditions of this study. S. frutescens also delays the production of midazolam metabolites in the hepatocytes, decreasing its clearance by 40%. Furthermore, S. frutescens inhibited P-gp (IC(50) = 324.8 µg/ml), OATP1B1 (IC(50) = 10.4 µg/ml), and OATP1B3 (IC(50) = 6.6 µg/ml). The result indicates the potential for HDI between S. frutescens and the substrates of the affected enzymes, if sufficient in vivo concentration of the extract is attained.

Authors+Show Affiliations

Division of Pharmacology, Department of Medicine, University of Stellenbosch, Tygerberg, Cape Town, South Africa. 16669967@sun.ac.zaNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

23209194

Citation

Fasinu, Pius S., et al. "The Potential of Sutherlandia Frutescens for Herb-drug Interaction." Drug Metabolism and Disposition: the Biological Fate of Chemicals, vol. 41, no. 2, 2013, pp. 488-97.
Fasinu PS, Gutmann H, Schiller H, et al. The potential of Sutherlandia frutescens for herb-drug interaction. Drug Metab Dispos. 2013;41(2):488-97.
Fasinu, P. S., Gutmann, H., Schiller, H., James, A. D., Bouic, P. J., & Rosenkranz, B. (2013). The potential of Sutherlandia frutescens for herb-drug interaction. Drug Metabolism and Disposition: the Biological Fate of Chemicals, 41(2), 488-97. https://doi.org/10.1124/dmd.112.049593
Fasinu PS, et al. The Potential of Sutherlandia Frutescens for Herb-drug Interaction. Drug Metab Dispos. 2013;41(2):488-97. PubMed PMID: 23209194.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The potential of Sutherlandia frutescens for herb-drug interaction. AU - Fasinu,Pius S, AU - Gutmann,Heike, AU - Schiller,Hilmar, AU - James,Alexander-David, AU - Bouic,Patrick J, AU - Rosenkranz,Bernd, Y1 - 2012/12/03/ PY - 2012/12/5/entrez PY - 2012/12/5/pubmed PY - 2013/7/16/medline SP - 488 EP - 97 JF - Drug metabolism and disposition: the biological fate of chemicals JO - Drug Metab. Dispos. VL - 41 IS - 2 N2 - In Africa, Sutherlandia frutescens is a popular medicinal herb widely consumed by people living with human immunodeficiency virus/AIDS. Concomitant use with antiretroviral drugs has generated concerns of herb-drug interaction (HDI). This study investigated the inhibitory effects of the crude extracts of S. frutescens on the major cytochrome P450 isozymes with the use of pooled human liver microsomes. Its effect on the metabolic clearance of midazolam using cryopreserved hepatocytes was also monitored. The potential of S. frutescens to inhibit human ATP-binding cassette transporters (P-gp and BCRP) and the human organic anion transporting polypeptide (OATP1B1 and OATP1B3) activity was assessed using cell lines overexpressing the transporter proteins. S. frutescens showed inhibitory potency for CYP1A2 (IC(50) = 41.0 µg/ml), CYP2A6 (IC(50) = 160 µg/ml), CYP2B6 (IC(50) = 20.0 µg/ml), CYP2C8 (IC(50) = 22.4 µg/ml), CYP2C9 (IC(50) = 23.0 µg/ml), CYP2C19 (IC(50) = 35.9 µg/ml), and CYP3A4/5 (IC(50) = 17.5 µg/ml [with midazolam1'-hydroxylation]; IC(50) = 28.3 µg/ml [with testosterone 6β-hydroxylation]). Time-dependent (irreversible) inhibition by S. frutescens was observed for CYP3A4/5 (K(I) = 296 µg/ml, k(inact) = 0.063 min(-1)) under the conditions of this study. S. frutescens also delays the production of midazolam metabolites in the hepatocytes, decreasing its clearance by 40%. Furthermore, S. frutescens inhibited P-gp (IC(50) = 324.8 µg/ml), OATP1B1 (IC(50) = 10.4 µg/ml), and OATP1B3 (IC(50) = 6.6 µg/ml). The result indicates the potential for HDI between S. frutescens and the substrates of the affected enzymes, if sufficient in vivo concentration of the extract is attained. SN - 1521-009X UR - https://www.unboundmedicine.com/medline/citation/23209194/The_potential_of_Sutherlandia_frutescens_for_herb_drug_interaction_ L2 - http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=23209194 DB - PRIME DP - Unbound Medicine ER -