*p < 0.05, **P<0.005 in comparison with group B.
Fig.1 UPLC-MS/MS chromatographs of tramadol, O-desmethyltramadol and IS (midazolam). (A) Blank plasma sample. (B) Blank plasma spiked with 100 ng mL-1tramadol, 25 ng mL-1 O-desmethyltramadol and 300 ng mL-1 IS. (C) Apatinib-treated rat plasma sample at 4h after tramadol.
Abbreviations: TIC, total ionic chromatography.
Fig.2. Apatinib with various concentrations for half-maximal inhibitory concentration (IC50) in the activity of (A) RLM, (B) HLM and (C) CYP2D6.1. Values are the mean ± SD, N = 3.
Fig.3. Primary Lineweaver–Burk plot, the secondary plot for Ki and the secondary plot for αKi in the inhibition of the metabolism of tramadol by various concentrations of apatinib in (A) RLM, (B) HLM and (C) CYP2D6.1. Values are mean ± SD, N = 3.
Fig.4. Mean concentration-time curve of tramadol and O-desmethyltramadol in the control group (tramadol alone) and the apatinib group (tramadol with apatinib) (N = 6).