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.