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Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats
Herein, the effect of silymarin pretreatment on the pharmacokinetics of simvastatin in rats was evaluated. To ensure the accuracy of the results, a rapid and sensitive UPLC–MS/MS method was established for simultaneous quantification of simvastatin (SV) and its active metabolite simvastatin acid (SV...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540003/ https://www.ncbi.nlm.nih.gov/pubmed/31035343 http://dx.doi.org/10.3390/molecules24091666 |
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author | Li, Ying Wu, Yin Li, Ya-Jing Meng, Lu Ding, Cong-Yang Dong, Zhan-Jun |
author_facet | Li, Ying Wu, Yin Li, Ya-Jing Meng, Lu Ding, Cong-Yang Dong, Zhan-Jun |
author_sort | Li, Ying |
collection | PubMed |
description | Herein, the effect of silymarin pretreatment on the pharmacokinetics of simvastatin in rats was evaluated. To ensure the accuracy of the results, a rapid and sensitive UPLC–MS/MS method was established for simultaneous quantification of simvastatin (SV) and its active metabolite simvastatin acid (SVA). This method was applied for studying the pharmacokinetic interactions in rats after oral co-administration of silymarin (45 mg/kg) and different concentrations of SV. The major pharmacokinetic parameters, including Cmax, tmax, t(1/2), mean residence time (MRT), elimination rate constant (λz) and area under the concentration-time curve (AUC(0–12h)), were calculated using the non-compartmental model. The results showed that the co-administration of silymarin and SV significantly increased the Cmax and AUC(0–12h) of SVA compared with SV alone, while there was no significant difference with regards to Tmax and t(1/2). However, SV pharmacokinetic parameters were not significantly affected by silymarin pretreatment. Therefore, these changes indicated that drug-drug interactions may occur after co-administration of silymarin and SV. |
format | Online Article Text |
id | pubmed-6540003 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65400032019-05-31 Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats Li, Ying Wu, Yin Li, Ya-Jing Meng, Lu Ding, Cong-Yang Dong, Zhan-Jun Molecules Article Herein, the effect of silymarin pretreatment on the pharmacokinetics of simvastatin in rats was evaluated. To ensure the accuracy of the results, a rapid and sensitive UPLC–MS/MS method was established for simultaneous quantification of simvastatin (SV) and its active metabolite simvastatin acid (SVA). This method was applied for studying the pharmacokinetic interactions in rats after oral co-administration of silymarin (45 mg/kg) and different concentrations of SV. The major pharmacokinetic parameters, including Cmax, tmax, t(1/2), mean residence time (MRT), elimination rate constant (λz) and area under the concentration-time curve (AUC(0–12h)), were calculated using the non-compartmental model. The results showed that the co-administration of silymarin and SV significantly increased the Cmax and AUC(0–12h) of SVA compared with SV alone, while there was no significant difference with regards to Tmax and t(1/2). However, SV pharmacokinetic parameters were not significantly affected by silymarin pretreatment. Therefore, these changes indicated that drug-drug interactions may occur after co-administration of silymarin and SV. MDPI 2019-04-28 /pmc/articles/PMC6540003/ /pubmed/31035343 http://dx.doi.org/10.3390/molecules24091666 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Li, Ying Wu, Yin Li, Ya-Jing Meng, Lu Ding, Cong-Yang Dong, Zhan-Jun Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats |
title | Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats |
title_full | Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats |
title_fullStr | Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats |
title_full_unstemmed | Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats |
title_short | Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats |
title_sort | effects of silymarin on the in vivo pharmacokinetics of simvastatin and its active metabolite in rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540003/ https://www.ncbi.nlm.nih.gov/pubmed/31035343 http://dx.doi.org/10.3390/molecules24091666 |
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