Integration of modern science into herbal medicine: application of pharmacokinetic-pharmacodynamic modeling in understanding nonclinical study of Cinnamomum cassia extract

• Published in: Journal of pharmaceutical investigation 2024, 54(6), , pp.803-815
• Main Authors: Kim, Ju Hee, Hong, Young Bean, Kang, Dong Wook, Cho, Seok-jin, Seo, Hye Jin, Cho, Hea-Young
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Original Article; 약학
• ISSN: 2093-5552; 2093-6214
• DOI: 10.1007/s40005-024-00683-w

Purpose CKD-495 is a tablet form of Cinnamomum cassia Presl extract (CCE), which is a commonly used herb in traditional medicine that exhibits several pharmacological effects including anti-gastritis activities. This study aimed to evaluate the nonclinical pharmacokinetic (PK) characteristics of the 4 major bioactive components in CCE—cinnamic acid—ferulic acid, 3,4-dihydroxy benzaldehyde, and 4-hydroxy cinnamaldehyde—when administered as a reference solution or CKD-495, a dried-powdered form of CCE, by using PK and pharmacokinetic-pharmacodynamic (PK-PD) modeling to interpret and to translate nonclinical results. Methods The animal study was conducted in male Sprague Dawley rats, and bioanalysis methods in plasma and 7 tissues were developed and validated according to the FDA bioanalysis guideline. Then, Phoenix NLME 8.3 software was used for the data analysis and modeling. Through the study, PK alterations between the major components’ reference solution and extract powder were observed. Allometric scaling and PK-PD modeling techniques were applied to simulate the effective bioactive component’s human plasma concentrations and the inhibition effect of the extract. Results The PK characteristics of the major bioactive components of CCE were captured in rats after the administration of reference solutions or three doses of CKD-495. After the administration of the reference solutions, the PK profiles of the four components were best described by two-compartment models with multiplicative residual error. After administration of CKD-495, PK parameters could be estimated for cinnamic acid and 4-hydroxy cinnamaldehyde. Then, the holistic PK model of the effective constituents (nM) linked with the indirect PD model was used to predict and simulate profiles in rats and humans. Conclusion Overall, this study proposed a method to provide scientific evidence to the emerging market of herbal medicines, using the CKD-495 case. In the future, this method could be used as a guide for PK characterization and rational dosing regimens of multi-component herbal medicines.