Alterations in the Pharmacokinetics of Paeoniflorin and Albiflorin in a Collagen‑Induced Arthritis Rat Model

Background: Rheumatoid arthritis (RA) is an autoimmune disease that seriously affects the patient’s quality of life. Total glucosides of peony (TGP) have long been used to treat RA in China despite the need for long‑term administration. The main active ingredients in TGP are paeoniflorin (PF) and albiflorin (AF). This study aimed to clarify the effective mechanism of TGP only after long‑term administration, and the pharmacokinetics of PF and AF following single and chronic oral TGP administration in collagen‑induced arthritic (CIA) and normal rats. Materials and Methods: Comparative pharmacokinetic studies of TGP were conducted in male Sprague Dawley rats. Plasma concentrations of PF and AF were determined with ultra‑high performance liquid chromatography– tandem mass spectrometry (UPLC‑MS/MS). DAS software was used to estimate pharmacokinetic parameters. Results: Bimodal phenomenon was observed. After a single TGP dose, the absorption of AF and PF were both lower in CIA rats compared to control rats. Compared with single‑dose groups, the absorption of AF and PF in CIA rats increased after long‑term administration of TGP. No significant differences were seen between the groups after chronic administration in low‑dose groups in normal rats. Conclusion: We found that after long‑term administration of TGP, the absorption of PF and AF are promoted in CIA rats. These results, combined with the existing literature, may help substantiate the TGP‑related changes in gut microbiota.