Metabolic characteristics and pharmacokinetic differences of Qiwei Tongbi oral liquid in rheumatoid arthritis rats

Abstract

Qiwei Tongbi oral liquid (QWTB), a classical traditional Chinese medicine formula, is widely used to treat arthritis‐related diseases in clinical practice. Currently, in vivo metabolic characteristics and pharmacokinetic studies are lacking. This study analyzed the prototype components of QWTB absorbed in the blood and their metabolic transformation process after intragastric administration and compared the differences in pharmacokinetic properties between healthy and rheumatoid arthritis model rats. In sum, 17 prototype components and 21 related metabolites were identified in the plasma and urine of the treated rats. Metabolites were derived from sinomenine and magnoflorine. Through systematic methodology verification, an accurate and stable detection method for sinomenine and magnoflorine in plasma samples was established and applied to pharmacokinetic research of QWTB. At the three dose levels, the AUC0–∞ (area under the curve) of the two components showed a good positive correlation with the dose (R2 > 0.9). Compared with healthy rats, the Tmax, t1/2z, and AUC of sinomenine were markedly increased, and Cmax was decreased in rheumatoid arthritis model rats, indicating that the rate of absorption and elimination rate decreased, but the body exposure increased. However, there were no significant differences in the pharmacokinetic parameters of magnoflorine under healthy and pathological conditions. In summary, the main active ingredients of QWTB are sinomenine and magnoflorine, which exhibit linear kinetic characteristics within a set dose range, and the rheumatoid arthritis pathological state is more conducive to the absorption and efficacy of sinomenine. The results of this study demonstrate the rationality of the clinical application of the QWTB.

Study on the liver Drug’s dominant metabolic enzymes for six effective components of the Huang qi Liuyi decoction

“…All remaining chemicals were of analytical grade. HQD was self-produced by the research group (Wang et al, 2022). The content of each component in HQD is shown in Table 1.…”

“…This allows for clear pharmacological effects, relatively stable nature, and can effectively compensate for the shortcomings of traditional prescriptions whose quality is not easily controlled (Wang and Liang, 2004;Hu et al, 2016;Chen et al, 2019). Previously, our team discovered that the combination of four components extracted from Huangqi Liuyi Decoction, namely, astragalus saponin, glycyrrhizic acid, astragalus flavone, and astragalus polysaccharide (AKA HQD), improved renal fibrosis and slowed the progression of diabetic nephropathy in db/db mice (Wang et al, 2022). The study also discovered no statistical difference between the efficacy of Huangqi Liuyi decoction and HQD in mice with diabetic nephropathy (Wang et al, 2022b).…”

“…The pathological state of the patient considerably influences drug-related processes in vivo, which directly relates to the drug's efficacy and side effects (Ma et al, 2021;Qian et al, 2022). The alterations in the pharmacokinetics of drug in DN may relate to the changes in the activity of a variety of CYP450 cytochrome (CYP) enzymes involved in drug absorption, metabolism, and excretion (Hu et al, 2014;Gong et al, 2015).…”

Liquid chromatography‐mass spectrometry‐based strategy for systematic profiling of chemical components and associated quantitative analysis of quality markers in Qi‐Wei‐Tong‐Bi oral liquid

“…Schott, and roots and rhizomes of Clematis chinensis Osbeck [1], and it has the effects of tonifying kidneys and strengthening bones, dispelling wind, and removing arthralgia. At present, this product, given alone or in combination, is clinically indicated to treat rheumatoid arthritis (RA) which is a syndrome characterized by liver and kidney deficiency and rheumatism-blocking collaterals [2][3][4]. For patients with stable long-standing RA, QWTB has been reported to have the potential to decrease inflammation and pain scores and then improve patients' outcomes [5].…”