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In Vitro Evaluation of the Potential for Drug Interactions by Salidroside

Several studies utilizing Rhodiola rosea, which contains a complex mixture of phytochemicals, reported some positive drug-drug interaction (DDI) findings based on in vitro CYP450’s enzyme inhibition, MAO-A and MAO-B inhibition, and preclinical pharmacokinetic studies in either rats or rabbits. Howev...

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Autores principales: Kasprzyk, Philip G., Tremaine, Larry, Fahmi, Odette A., Weng, Jing-Ke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10489644/
https://www.ncbi.nlm.nih.gov/pubmed/37686755
http://dx.doi.org/10.3390/nu15173723
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author Kasprzyk, Philip G.
Tremaine, Larry
Fahmi, Odette A.
Weng, Jing-Ke
author_facet Kasprzyk, Philip G.
Tremaine, Larry
Fahmi, Odette A.
Weng, Jing-Ke
author_sort Kasprzyk, Philip G.
collection PubMed
description Several studies utilizing Rhodiola rosea, which contains a complex mixture of phytochemicals, reported some positive drug-drug interaction (DDI) findings based on in vitro CYP450’s enzyme inhibition, MAO-A and MAO-B inhibition, and preclinical pharmacokinetic studies in either rats or rabbits. However, variation in and multiplicity of constituents present in Rhodiola products is a cause for concern for accurately evaluating drug-drug interaction (DDI) risk. In this report, we examined the effects of bioengineered, nature-identical salidroside on the inhibition potential of salidroside on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 utilizing human liver microsomes, the induction potential of salidroside on CYP1A2, CYP2B6 and CYP3A4 in cryopreserved human hepatocytes, the inhibitory potential of salidroside against recombinant human MAO-A and MAO-B, and the OATP human uptake transport inhibitory potential of salidroside using transfected HEK293-OATP1B1 and OATP1B3 cells. The results demonstrate that the bioengineered salidroside at a concentration exceeding the predicted plasma concentrations of <2 µM (based on 60 mg PO) shows no risk for drug-drug interaction due to CYP450, MAO enzymes, or OATP drug transport proteins. Our current studies further support the safe use of salidroside in combination with other drugs cleared by CYP or MAO metabolism or OATP-mediated disposition.
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spelling pubmed-104896442023-09-09 In Vitro Evaluation of the Potential for Drug Interactions by Salidroside Kasprzyk, Philip G. Tremaine, Larry Fahmi, Odette A. Weng, Jing-Ke Nutrients Article Several studies utilizing Rhodiola rosea, which contains a complex mixture of phytochemicals, reported some positive drug-drug interaction (DDI) findings based on in vitro CYP450’s enzyme inhibition, MAO-A and MAO-B inhibition, and preclinical pharmacokinetic studies in either rats or rabbits. However, variation in and multiplicity of constituents present in Rhodiola products is a cause for concern for accurately evaluating drug-drug interaction (DDI) risk. In this report, we examined the effects of bioengineered, nature-identical salidroside on the inhibition potential of salidroside on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 utilizing human liver microsomes, the induction potential of salidroside on CYP1A2, CYP2B6 and CYP3A4 in cryopreserved human hepatocytes, the inhibitory potential of salidroside against recombinant human MAO-A and MAO-B, and the OATP human uptake transport inhibitory potential of salidroside using transfected HEK293-OATP1B1 and OATP1B3 cells. The results demonstrate that the bioengineered salidroside at a concentration exceeding the predicted plasma concentrations of <2 µM (based on 60 mg PO) shows no risk for drug-drug interaction due to CYP450, MAO enzymes, or OATP drug transport proteins. Our current studies further support the safe use of salidroside in combination with other drugs cleared by CYP or MAO metabolism or OATP-mediated disposition. MDPI 2023-08-25 /pmc/articles/PMC10489644/ /pubmed/37686755 http://dx.doi.org/10.3390/nu15173723 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kasprzyk, Philip G.
Tremaine, Larry
Fahmi, Odette A.
Weng, Jing-Ke
In Vitro Evaluation of the Potential for Drug Interactions by Salidroside
title In Vitro Evaluation of the Potential for Drug Interactions by Salidroside
title_full In Vitro Evaluation of the Potential for Drug Interactions by Salidroside
title_fullStr In Vitro Evaluation of the Potential for Drug Interactions by Salidroside
title_full_unstemmed In Vitro Evaluation of the Potential for Drug Interactions by Salidroside
title_short In Vitro Evaluation of the Potential for Drug Interactions by Salidroside
title_sort in vitro evaluation of the potential for drug interactions by salidroside
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10489644/
https://www.ncbi.nlm.nih.gov/pubmed/37686755
http://dx.doi.org/10.3390/nu15173723
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