1. Pharmacokinetic-pharmacodynamic modeling analysis and anti-inflammatory effect of Wangbi capsule in the treatment of adjuvant-induced arthritis.
- Author
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Liu T, Zhao M, Zhang Y, Qiu Z, Zhang Y, Zhao C, and Wang M
- Subjects
- Animals, Benzopyrans blood, Benzopyrans pharmacokinetics, Bridged-Ring Compounds blood, Bridged-Ring Compounds pharmacokinetics, Disease Models, Animal, Flavonoids blood, Flavonoids pharmacokinetics, Freund's Adjuvant adverse effects, Glucosides blood, Glucosides pharmacokinetics, Joints drug effects, Joints metabolism, Male, Medicine, Chinese Traditional, Monoterpenes blood, Monoterpenes pharmacokinetics, Rats, Rats, Sprague-Dawley, Anti-Inflammatory Agents administration & dosage, Anti-Inflammatory Agents chemistry, Anti-Inflammatory Agents pharmacokinetics, Anti-Inflammatory Agents pharmacology, Arthritis, Experimental drug therapy, Arthritis, Experimental metabolism, Drugs, Chinese Herbal administration & dosage, Drugs, Chinese Herbal chemistry, Drugs, Chinese Herbal pharmacokinetics, Drugs, Chinese Herbal pharmacology
- 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-1β and prostaglandin E2 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 E2 and interleukin-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 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., (© 2021 John Wiley & Sons, Ltd.)- Published
- 2021
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