Influence of Gegenqinlian Decoction on Pharmacokinetics and Pharmacodynamics of Atorvastatin Calcium in Hyperlipidemic Rats

Abstract

Background and Objectives Gegenqinlian decoction (GQD), a classic traditional Chinese medicine (TCM), was described in Shanghan Lun. GQD is often combined with antihyperlipidemic drugs (mainly atrovastatin calcium) in TCM clinics. However, the herb-drug interaction between GQD and atrovastatin calcium (AC) is still unknown. To determine whether the combination is safe, we evaluated the effects of GQD on the activities of cytochrome P450 (CYP) 3A2 enzyme and investigated the impact of GQD on the pharmacokinetics and pharmacodynamics of AC in rats. Methods The pharmacokinetics of AC (10 mg/kg) with or without pretreatment with GQD (freeze-dried powder, 1.35 g/ kg) were investigated using HPLC. The influence of GQD on pharmacodynamics of AC were determined by detecting the levels of serum total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Moreover, the probe drug method was used to explore the effect of GQD on CYP3A2 activity. ResultsThe pharmacokinetic parameters of AC combined with GQD were significantly affected (P < 0.05) in hyperlipidemic rats. The serum TC, TG and LDL-C levels of the combination were significantly reduced (P < 0.05), and the serum HDL-C level was significantly increased (P < 0.05) compared with AC/GQD alone. AST and ALT activities treated with both GQD and AC+GQD group were significantly reduced (P < 0.05) compared with AC group. There was a significant difference in the pharmacokinetic parameters of midazolam between control and GQD groups (P < 0.05). Maximum concentration (C max ), area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration (AUC 0-t ) and AUC from time 0 to infinity (AUC 0-∞ ) increased significantly in GQD group. Conclusions The result suggested that GQD combined with AC can improve the lipid-lowering effect of AC and reduce the damage of AC to the liver simultaneously. However, GQD can inhibit the activity of CYP3A2 in hyperlipidemic rats and increase the blood concentration of AC. Therefore, the clinical dose of AC should be adjusted when they are combined. Since the study was conducted in rats, further research should be carried out to assess the uniformity of the pharmacokinetics and pharmacodynamics between rats and humans.

The in vivo study on antioxidant activity of wendan decoction in treating hyperlipidemia: a pharmacokinetic-pharmacodynamic (PK-PD) model

“…( Chaudhary and Dion, 2013 ). On the other hand, PD analysis analyzes the drug effect and the mechanism of action of a new drug ( Cui et al, 2022 ). In order to understand the connection of particular components in a complex preparation with efficacy or toxicity, the precise study of the PK-PD relationship is valuable, Flavonoids have been proven to exert the protective effects, including antioxidant and anti-inflammatory effects, by eliminating the free radicals ( Rajendran et al, 2004 ; Nauser and Gebicki, 2019 ; Kejík et al, 2021 ).…”

Influence of Gegenqinlian decoction on pharmacokinetics and pharmacodynamics of saxagliptin in type 2 diabetes mellitus rats

“…The filtrate was lyophilized further. The freeze‐dried powder of GQD was dissolved with 0.5% CMC‐Na before administration (1.35 g/kg of freeze‐dried powder equivalent to 3.5 g/kg of crude drugs) (Cui et al., 2022).…”

“…could affect the activity of CYP450 and transporter, which might cause HDIs (Kong et al., 2018; Liu et al., 2021; Wang et al., 2016). In our previous study, it was found that GQD could inhibit the activity of CPY3A2 in rats, increase the plasma exposure of atorvastatin when coadministrated in hyperlipidemic rats (Cui et al., 2022).…”