title: Potential accumulation of protopanaxadiol-type ginsenosides in six-months toxicokinetic study of SHENMAI injection in dogs.
abstract: SHENMAI injection (SMI), derived from famous Shen Mai San, is a herbal injection widely used in China. Ginsenosides are the major components of SMI. To monitor the exposure level of SMI during long-term treatment, a 6-month toxicokinetic experiment was performed. Twenty-four beagle dogs were dived into four groups (n = 6 in each group): a control group (0.9% NaCl solution) and three SMI groups (2, 6 or 3 mg/kg). The dogs were i.v. infused with vehicle or SMI daily for 180 d. Blood samples for analysis were collected at specific time points as follows: pre-dose (0 h); at 10, 30, and 60 min during infusion; and at 10, 30, 60, 90, 120, 240, and 300 min post-administration. Concentrations of ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1 in the plasma were determined simultaneously by liquid chromatography-tandem mass spectrometry. Non-compartmental parameters were further calculated and analyzed. Significant differences were found between the kinetic behavior of 20(S)-protopanaxadiol-type (PPD-type) and 20(S)-protopanaxatriol-type (PPT-type) ginsenosides. Increasing in the exposure level of PPD-type ginsenosides was observed in dogs during the experiment. Therefore, PPD-type ginsenosides are closely related to the immunity modulation effect of SMI. Increased PPD-type ginsenoside exposure level may present potential toxicity and induce drug-drug interaction risks during SMI administration. As such, PPD-type ginsenoside accumulation must be carefully monitored in future SMI research.
authors.affiliation: Center of Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.affiliation: Center of Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China.
authors.forename: Li-Qiang
authors.initials: LQ
authors.lastname: Gu
authors.affiliation: Center of Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China. Electronic address: xinyanfei@gmail.com.
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Xin
authors.affiliation: Beijing Space Odyssey Biotechnology Co., Ltd., Beijing, China.
authors.forename: Yun-Sheng
authors.initials: YS
authors.lastname: Bai
authors.affiliation: Center of Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Center of Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Gao
authors.affiliation: Center of Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China.
authors.forename: Pan-Sheng
authors.initials: PS
authors.lastname: Xu
authors.affiliation: Chiatai QingChunbao Pharmaceutical Co., Ltd., Hangzhou, Zhejiang, China.
authors.forename: Zhu-Feng
authors.initials: ZF
authors.lastname: Ma
authors.affiliation: Center of Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China.
authors.forename: Zhen-Qiang
authors.initials: ZQ
authors.lastname: You
authors.affiliation: Chiatai QingChunbao Pharmaceutical Co., Ltd., Hangzhou, Zhejiang, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Center of Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China.
authors.forename: Yao-Xian
authors.initials: YX
authors.lastname: Xuan
mesh_terms: D000818:Animals; D001822:Body Burden; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D036145:Ginsenosides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D007262:Infusions, Intravenous; D008297:Male; D008954:Models, Biological; D015203:Reproducibility of Results; D012502:Sapogenins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D066007:Toxicokinetics
chemical_list: D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D012502:Sapogenins; C009252:fructus schizandrae, radix ginseng, radix ophiopogonis drug combination; C062916:protopanaxadiol
keywords: Dogs; LC–MS/MS; Protopanaxadiol-type ginsenosides; Protopanaxatriol-type ginsenosides; SHENMAI injection; Toxicokinetics