Fig. 2.

To study if pharmacokinetics of sinominine (SN) in plasma and brain share similar characteristics, we continuously collected samples (using microdialysis), and detected SN concentrations in striatum of the brain (extracellular levels, A) and the blood (B). N = 2–3 rats for each group. Data was presented as Mean ± SEM. Following SN (50mg/kg, intravenous) single or repeated administrations (once per day for 3 days, detecting samples were collected after last injection at day 3). Under single SN administration, SN concentrations was higher in blood than in brain. Also, SN concentrations in blood and brain followed similar trend, which was illustrated by sharp reduction and almost completely cleared in around 6 h from 5150.65 ± 1212.09 (Mean ± SD) ng/ml at 0 h to 17.72 ± 12.53 (Mean ± SD) ng/ml at 6 h in plasma; and from 456.63 ± 88.48 (Mean ± SD) ng/ml at 0 h to 4.15 ± 2.07 (Mean ± SD) ng/ml at 6 h in extracellular striatal tissue; SN concentrations at 6 h in plasma or extracellular striatal tissue are considered as ultralow levels). Following repeated SN administration, SN concentrations resembled the trend of the single dose application (green square versus black circle, A), with SN concentrations sharply reduced from 397.17 ± 61.97 (Mean ± SD) ng/ml at 0 h to 49.79 ± 40.01 (Mean ± SD) ng/ml at 6 h in extracellular striatal tissue. The data showed that sinomenine could be cleared in around 6 h after drug application, and even there is uncleared drugs remained before first drug application at each day, the concentrations should be at ultralow level. There is no chance to generate drug accumulation of SN by repeated dosing especially in the targeted tissue (Brian), which is confirmed by testing SN's brain concentration under repeated dosages (A). The elevated baseline discovered in our pharmacological study [1], is more likely to be related to the pharmacodynamics effects than pharmacokinetics effects of the repeated drug combination.