Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Ying, Wu, Yin, Li, Ya-Jing, Meng, Lu, Ding, Cong-Yang, Dong, Zhan-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783422522865221632
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
work_keys_str_mv AT liying effectsofsilymarinontheinvivopharmacokineticsofsimvastatinanditsactivemetaboliteinrats
AT wuyin effectsofsilymarinontheinvivopharmacokineticsofsimvastatinanditsactivemetaboliteinrats
AT liyajing effectsofsilymarinontheinvivopharmacokineticsofsimvastatinanditsactivemetaboliteinrats
AT menglu effectsofsilymarinontheinvivopharmacokineticsofsimvastatinanditsactivemetaboliteinrats
AT dingcongyang effectsofsilymarinontheinvivopharmacokineticsofsimvastatinanditsactivemetaboliteinrats
AT dongzhanjun effectsofsilymarinontheinvivopharmacokineticsofsimvastatinanditsactivemetaboliteinrats