Pharmacokinetic‐pharmacodynamic (PK‐PD) Modeling Analysis and Anti‐inflammatory Effect of WangBi Capsule in the Treatment of Adjuvant‐Induced Arthritis

Published on Feb 24, 2021in Biomedical Chromatography1.728
· DOI :10.1002/BMC.5101
Tingting Liu1
Estimated H-index: 1
(SPU: Shenyang Pharmaceutical University),
Min Zhao8
Estimated H-index: 8
(SPU: Shenyang Pharmaceutical University)
+ 4 AuthorsMiao Wang9
Estimated H-index: 9
(SPU: Shenyang Pharmaceutical University)
Source
Abstract
Clinically, Wangbi Capsule (WBC) is widely used in the treatment of Rheumatoid arthritis (RA) because of its remarkable therapeutic effect. To reveal the mechanism, a pharmacokinetic-pharmacodynamic (PK-PD) model was developed for the first time to assess the relationship between time-concentration (dose)-effect. Freund's Complete Adjuvant (FCA) was used to induce the Adjuvant-Induced Arthritis (AIA) model. Multi-index were used to evaluate the therapeutic effect and a S-Imax PK-PD model was established based on the concentrations of osthole, 5-O-methylvisamminoside, cimifugin, albiflorin, paeoniflorin and icariin and the levels of IL-1β and PGE2 using a two-compartment PK model together with a PD model with an effect-site compartment. The results have suggested that WBC can treat RA by regulating the levels of PGE2 and IL-1β. For the PK-PD model, the parameters indicated that WBC had a large safety margin and all six bioactive ingredients of WBC have therapeutic effects on RA. Among which icariin, osthole and 5-O-methylvisamminoside may be the main effective substances. This study provided a scientific basis for further study of PPK/PPD, to develop a reasonable administration plan and improve the level of the individualized drug.
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