Safety, tolerability and pharmacokinetics of a Class I natural medicine with therapeutic potential for vascular dementia: Naoqingzhiming tablet.

Naoqingzhiming, whose active ingredient is echinacoside, is the first new Class I natural medicine approved for clinical trials for the therapeutic potential of vascular dementia in China. We report randomized, double-blind, placebo-controlled trials to evaluate the safety, tolerability and pharmacokinetics of single ascending doses of Naoqingzhiming tablet after oral administration in healthy Chinese subjects. The single ascending dose of Naoqingzhiming tablet (180-2160 mg) were well tolerated in all enrolled subjects, without serious adverse events and adverse events leading to withdrawal from the study. The most common drug-related treatment-emergent adverse events were elevated blood bilirubin and serum uric acid. No clinically significant findings were found in the physical examinations, vital signs or electrocardiograms. After single-dose administration of Naoqingzhiming tablet, echinacoside was absorbed with a T _max at 1.25-1.75 h and declined with a t _1/2 of 2.42-3.33 h. However, the proportionality coefficients for C _max , AUC _0-t and AUC _0-∞ of echinacoside were not fully contained in the pre-defined 90 % CI criterion (0.91-1.09). As a result, the dose proportionality could not be concluded statistically within the dosage range of this study. Overall, the safety profile and PK properties support further development and use of Naoqingzhiming in vascular dementia.
Competing Interests: Conflicts of Interest Statement Mingxia Chen, Haiyan Jiang, Fanli Yan and Yahui Han are employees of Beijing Scrianen Pharmaceutical Co., Ltd. Other authors declare no conflicts of interest.
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