Disposition and tissue distribution of imatinib in a liposome formulation after intravenous bolus dose to mice

Imatinib is an efficacious anticancer drug with a spectrum of potential antitumour applications limited by poor biodistribution at therapeutic concentrations to the tissues of interest.  We assess the pharmacokinetic and tissue distribution profile of imatinib in a liposome formulation.  Its single dose (6.25 mg·kg⁻¹) in a liposome formulation was administered iv to male mice.  Imatinib concentration was measured in plasma, spleen, liver, kidney and brain using a HPLC assay.  Non-compartmental pharmacokinetic approach was used to assess the disposition parameters.  The plasma disposition profile was biphasic with a plateau-like second phase.  The AUC_0→∞ was 11.24 μg·h·mL⁻¹, the elimination rate constant (k_el) was 0.348 h⁻¹ and the elimination half life (t_1/2) was 2.0 h.  The mean residence time (MRT) was 2.59 h, V_SS was 1.44 L·kg⁻¹ and clearance was 0.56 L·h·kg⁻¹.  Liver achieved the highest tissue exposure: C_MAX = 18.72 μg·mL⁻¹; AUC_0→∞ = 58.18 μg·h·mL⁻¹ and longest t_1/2 (4.29 h) and MRT (5.31 h).  Kidney and spleen AUC_0→∞ were 47.98 μg·h·mL⁻¹ and 23.46 μg·h·mL⁻¹, respectively.  Half-life was 1.83 h for the kidney and 3.37 h for the spleen.  Imatinib penetrated into the brain reaching ~1 μg·g⁻¹.  Upon correction by organ blood flow the spleen showed the largest uptake efficiency.   Liposomal imatinib presented extensive biodistribution.  The drug uptake kinetics showed mechanism differences amongst the tissues.  These findings encourage the development of novel imatinib formulations to treat other cancers.