Pharmaceutical Properties of Rikkunshito Extract Suppository and Bioequivalence by Pharmacokinetic Parameters and Effectiveness against Nausea and Vomiting and Anorexia in Rats

Abstract

In patients with cancer, it is difficult to continue medical treatment owing to nausea and vomiting (NV). Therefore, it is important to avoid these problems for improving the patient's QOL. Rikkunshito extract (RK) possesses antiemetic effects and is used in combination in cancer therapy. However, patients with cancer find it difficult to take the medicine orally for the treatment of NV and anorexia owing to the characteristic smell and taste of traditional Chinese medicine. We examined the pharmaceutical properties of RK suppository for hospital use, assessed bioequivalence by using pharmacokinetic parameters, and determined its effectiveness against NV and anorexia in rats. In this study, RK suppository was prepared by using RK formulation (A, B, and C) and Witepsol (H and S) (AH, BH, CH, AS, BS, and CS). Pharmaceutical properties, namely, hardness, dispersibility, long-term stability, and drug (hesperidin and glycyrrhizic acid) release were measured for AH, BH, AH, and AS. The pharmacokinetic parameters, effectiveness of substance P against NV and anorexia, and serotonin-activated ghrelin levels were assessed for BH only. AH, BH, AS, and AS demonstrated uniform and sufficient hardness. The release rate of oleaginous components, such as glycyrrhizic acid, did not change significantly, while that of water soluble components, such as hesperidin, decreased when compared with that in powder formulations A and B. NV and anorexia improved in rats administered BH compared with the control group. BH suppository showed effectiveness in terms of both physicochemical property and bioequivalence for hospital use.