Lack of dose dependent kinetics of methyl salicylate-2-O-β-d-lactoside in rhesus monkeys after oral administration. (22nd April 2015)

• Record Type: Journal Article
• Authors: He, Yangyang; Yan, Yu; Zhang, Tiantai; Ma, Yinzhong; Zhang, Wen; Wu, Ping; Song, Junke; Wang, Shuang; Du, Guanhua
• Is Part Of: Journal of ethnopharmacology. Volume 164(2015)
• Page Start: 293
• Page End: 300
• Publication Date: 2015-04-22
• Subjects: MSL methyl salicylate-2-O-β-d-lactoside -- SA salicylic acid -- CIA collagen-induced arthritis -- HPLC high performance liquid chromatography -- UV ultraviolet -- CDE Center for Drug Evaluation -- SFDA China׳s State Food and Drug Administration -- IS internal standard -- QC quality control -- LLOQ lower limit of quantification -- AUC area under the plasma concentration-time curve -- RSD relative standard deviation -- Cmax mean maximum concentration -- T1/2 half-life elimination -- Tmax time to reach Cmax -- MRT mean residence time -- CL clearance rate -- Fapp apparent absolute oral bioavailability; Methyl salicylate-2-O-β-d-lactoside -- HPLC -- Pharmacokinetics -- Bioavailability -- Salicylic acid; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2014.12.063
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Methyl salicylate-2-O- β -d -lactoside (MSL) is one of the main active components isolated from Gaultheria yunnanensis, which is a traditional Chinese medicine used to treat arthritis and various aches and pains. Pharmacological researches showed that MSL had various effective activities in both in vivo and in vitro experiments. However, the pharmacokinetics features and oral bioavailability of MSL in primates were not studied up to now. Aim: To study the pharmacokinetics of different doses of MSL in rhesus monkeys and investigate the absolute bioavailability of MSL after oral administration. Materials and methods: Male and female rhesus monkeys were either orally administrated with MSL 200, 400 and 800 mg/kg or received an intravenous dose of 20 mg/kg randomly. The levels of MSL and salicylic acid (SA) in plasma were simultaneous measured by a simple, sensitive and reproducible high performance liquid chromatography method. Results: Mean peak plasma concentration values for groups treated with 200, 400 and 800 mg/kg doses ranged from 48.79 to 171.83 μg/mL after single-dose oral administration of MSL, and mean area under the concentration–time curve values ranged from 195.16 to 1107.76 μg/mL h. Poor linearity of the kinetics of SA after oral administration of MSL was observed in the regression analysis of the C max -dose plot ( r 2 =0.812), CL-dose plot ( r 2 =0.225) and AUC(0− t ) -dose plot ( r 2 =0.938). Absolute bioavailability of MSL was assessed to be 118.89±57.50, 213.54±58.98 and 168.72±76.58%, respectively. Conclusions: Bioavailability of MSL after oral administration in rhesus monkeys was measured for the first time. Pharmacokinetics parameters did not appear to be dose proportional among the three oral doses of treatments, and MSL showed an apparent absolute bioavailability in excess of 100% in rhesus monkeys based on the present study. In addition, a rapid, sensitive and reliable HPLC method was established and demonstrated for the research of traditional Chinese medicine in this study. Graphical abstract: