2.8 Effect of ningetinib on the pharmacokinetics of D6-M1 in
mice.
Fourteen healthy male ICR mice were randomly divided into treatment and
control groups. They were fasted for 12 h with free access to water
before the experiments. In the treatment group, ningetinib (40
mg·kg-1, suspended in 0.5% CMC-Na solution; This dose
design considered the high initial blood concentration of D6-M1 when
administered intravenously.) was administrated to mice by gavage 30 min
in advance, and then, D6-M1 (0.5 mg·kg-1, dissolved in
saline containing 5% DMSO and 5% Tween 80) was given through tail vein
injection. In the control group, the same volume of 0.5% CMC-Na
solution (10 mL·kg-1) without ningetinib was orally
administered. Then, 30 min later D6-M1 (0.5 mg·kg-1)
was injected intravenously. Blood samples (5 μL for each) were collected
through the tail vein and placed in test tubes containing 30 μL of 0.1 M
trisodium citrate solution before administration (0 h) and 0.083, 0.25,
0.5, 1, 2, 4, 6, 8, 12, 24 and 48 h after administration of D6-M1. Blood
samples were stored at -20 °C until LC-MS/MS analysis.