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

Abstract

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, t1/2, mean residence time (MRT), elimination rate constant (λz) and area under the concentration-time curve (AUC0–12h), were calculated using the non-compartmental model. The results showed that the co-administration of silymarin and SV significantly increased the Cmax and AUC0–12h 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.

Formulation and optimization of drug-loaded mesoporous silica nanoparticle-based tablets to improve the dissolution rate of the poorly water-soluble drug silymarin

“…In this synthesis approach, the pore diameter can be controlled according to the concentration of both hydrophobic solvents and silica source (Li et al, 2014). The model drug used in our study is silymarin (SLM); used mostly as a hepatoprotective drug albeit with other potential therapeutic activities, for instance anticancer, anti-oxidation, antiinflammation as well as for the treatment of Alzheimer's disease (AD) (Guo et al, 2019) (Li et al, 2019) (Kren and Walterová, 2005). However, SLM is characterized by low aqueous solubility and poor permeation across the intestinal fluid.…”

Systematic review of pharmacokinetics and potential pharmacokinetic interactions of flavonolignans from silymarin

“…The AUC and C max of ivabradine increased, which can strongly suggest the inhibition of CYP3A4, but if the theory is true, the same parameters of desmethylivabradine should decrease, but no changes in the pharmacokinetics of this metabolite were found 249 . Similarly, the plasma levels of a known substrate of CYP3A4, simvastatin, were not significantly affected by the administration of even very high doses of silymarin, but its active metabolite was increased 256 . It is highly possible that instead of inhibition of P‐glycoprotein, other efflux transporters, conjugation, and possibly also some unknown pharmacokinetic factors can contribute to the observed effects.…”