Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats

Autor: Ya-Jing Li, Lu Meng, Zhan-Jun Dong, Cong-Yang Ding, Ying Li, Yin Wu
Jazyk: angličtina
Rok vydání: 2019
Předmět:
silymarin
Cmax
Pharmaceutical Science
Pharmacology
030226 pharmacology & pharmacy
High-performance liquid chromatography
Article
Analytical Chemistry
lcsh:QD241-441
03 medical and health sciences
0302 clinical medicine
herb-drug interaction
Pharmacokinetics
Elimination rate constant
lcsh:Organic chemistry
Drug Discovery
medicine
polycyclic compounds
Animals
Metabolomics
simvastatin
Drug Interactions
Physical and Theoretical Chemistry
Active metabolite
Molecular Structure
Chemistry
Organic Chemistry
nutritional and metabolic diseases
simvastatin hydroxyacid
Rats
Chemistry (miscellaneous)
Simvastatin acid
Simvastatin
030220 oncology & carcinogenesis
Molecular Medicine
lipids (amino acids
peptides
and proteins)
Hydroxymethylglutaryl-CoA Reductase Inhibitors
pharmacokinetics
In vivo pharmacokinetics
medicine.drug
Zdroj: Molecules, Vol 24, Iss 9, p 1666 (2019)
Molecules
Volume 24
Issue 9
ISSN: 1420-3049
Popis: 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&ndash
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, t1/2, mean residence time (MRT), elimination rate constant (&lambda
z) and area under the concentration-time curve (AUC0&ndash
12h), were calculated using the non-compartmental model. The results showed that the co-administration of silymarin and SV significantly increased the Cmax and AUC0&ndash
12h of SVA compared with SV alone, while there was no significant difference with regards to Tmax and t1/2. 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.
Databáze: OpenAIRE
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