Pharmacokinetic effects of metformin hydrochloride, food and alcohol on Ramulus Mori (Sangzhi) alkaloids
10.16438/j.0513-4870.2023-0354
- VernacularTitle:盐酸二甲双胍、食物和乙醇对桑枝总生物碱药代动力学的影响
- Author:
Hang ZHAO
1
;
Yu FENG
2
;
Wen-ming JI
3
;
Li WANG
2
;
Zhi-hua LIU
2
;
Jing-han YU
1
;
Jia-ling CHENG
1
;
Jun YE
1
;
Xue-jun XIA
1
;
Yu-ling LIU
1
Author Information
1. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
2. Beijing Wehand-Bio Pharmaceutical Co., Ltd., Beijing 102600, China
3. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:Research Article
- Keywords:
Ramulus Mori (Sangzhi) alkaloid;
metformin hydrochloride;
rug interaction;
pharmacokinetics;
food and alcohol
- From:
Acta Pharmaceutica Sinica
2023;58(12):3674-3683
- CountryChina
- Language:Chinese
-
Abstract:
Ramulus Mori (Sangzhi) alkaloids (SZ-A) are a group of polyhydroxy alkaloids extracted and isolated from the traditional Chinese medicine mulberry twig, which is mainly used for the treatment of type 2 diabetes mellitus (T2DM). In addition to acting as a glycosidase inhibitor in the small intestine after oral administration, SZ-A can also be absorbed into blood and widely distributed to target organs related to diabetes, exerting multiple pharmacological effects. It is important to elucidate the possible pharmacokinetic influences of SZ-A for its clinical rational applications, such as drug interactions, the effects of food and alcohol on the absorption of SZ-A. However, studies in this area are limited. Therefore, the pharmacokinetic interactions between orally administrated SZ-A (50 mg·kg-1) and metformin hydrochloride (Met, 200 mg·kg-1) in Sprague-Dawley (SD) rats were examined. Then, the effect of food (standard feed) on the pharmacokinetics of SZ-A was investigated using fasting administration of SZ-A (50 mg·kg-1) in rats as a control. Finally, we investigated the pharmacokinetic characteristics of SZ-A (50 mg·kg-1) in different concentrations alcohol solutions using aqueous solution of SZ-A administered to rats as a control to evaluate the effect of alcohol on the bioabsorption of SZ-A. The results showed no significant pharmacokinetic interactions between SZ-A and Met after combination treatment. The standard feed had little effect on the pharmacokinetic profile of SZ-A. Alcohol retarded the absorption of SZ-A, resulting in a significant decrease in the Cmax of SZ-A. The decrease was greater at higher alcohol concentrations; however, no significant difference was observed in the AUC0-t. These results support the clinical rational applications of SZ-A. All animal protocols were approved by the Ethics Committee of Kangtai Medical Laboratory Service Hebei Co., Ltd. (Hebei, China) (No. MDL2022-01-17-1).
