000001b5_王庆伟-应用药理.docVIP

A Dose-dependent Pharmacokinetic Study of a Candidate Anti-fatigue Drug: Tyrosol Galactoside Qingwei Wanga,1, Yating Dengb,1, Xueying Liuc*, Yu Wangc, Zijie Dingc aDepartment of Pharmacy,The Second Affiliated Hospital, Fourth Military Medical University, Xi’an710038, PR China b Department of Pharmacology, Fourth Military Medical University, Xi’an 710032, PR China cDepartment of Medicinal Chemistry, Fourth Military Medical University, 17 Changlexi Street, Xi’an 710032, PR China *Corresponding author at Department of Medicinal Chemistry, Fourth Military Medical University, 17 Changlexi Street, Xi’an 710032, PR China. Tel: +86 8477- 4473 Fax: +86 8477 - 6845 E-mail address: wqwlxy@fmmu.edu.cn 1These authors contributed equally to this work. Abstract: Tyrosol Galactoside (TG) is a new candidate anti-fatigue agent under development. It was designed using computational modeling based on a naturally occurring salidroside. Previous studies have shown the drug has promising anti-fatigue activity and unremarkable toxicity. In order to have a good understanding of its pharmacokinetic characters, the paper described dose-dependent pharmacokinetics of TG in rats after oral and intravenous administration. TG was rapidly absorbed after oral administration and cleared with first-order rate, for the plasma half-life was independent of dose. Cmax and AUC0–∞ after both intravenous and oral dosing were all liner correlated with dose, as regression correlation coefficient (R) was 0.998, 0.989 and 0.994 for AUC0–∞ (iv, P 0.01) AUC0–∞ (ig, P 0.01) and Cmax (ig, P 0.01), respectively. However, these parameters increased less than proportionally with increasing dose. In addition, the apparent volume of distribution (Vd) and the apparent clearance (Cl) seemed to be affected by dose. 1. Introduction Fatigue is one of the most frequent and most disabling nonmotor problems in both sick and healthy individuals, which may result in multi-system dysfunctions (mainly involving the neuroendocrin