Pharmacokinetic–pharmacodynamic modeling analysis and anti‐inflammatory effect of Wangbi capsule in the treatment of adjuvant‐induced arthritis

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 was used to induce the adjuvant‐induced arthritis model. Multi‐indices were used to evaluate the therapeutic effect and an S‐I max PK–PD model was established based on the concentrations of osthole, 5 ‐O‐ methylvisamminoside, cimifugin, albiflorin, paeoniflorin and icariin and the levels of interleukin‐1 β and prostaglandin E 2 using a two‐compartment PK model together with a PD model with an effect‐site compartment. The results suggest that WBC can treat RA by regulating the levels of prostaglandin E 2 and interleukin‐1 β . 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 them icariin, osthole and 5 ‐O‐ methylvisamminoside may be the main effective substances. This study provided a scientific basis for further study of population pharmacokinetics / population pharmacodynamics (PPK/PPD), to develop a reasonable administration plan and improve individualized drug therapy.