Pharmacokinetic/metric parameters estimated from NCA of total brain and plasma concentration-time profiles after administration of a single intravenous bolus of ponatinib (3 mg/kg) in FVB wild-type and Mdr1a/b(−/−)Bcrp1(−/−) mice (N = 3 to 4 at each time point)

Data are presented as mean or mean ± S.E.M, unless otherwise indicated.

FVB Wild-TypeMdr1a/b(−/−)Bcrp1(−/−)FVB Wild-TypeMdr1a/b(−/−)Bcrp1(−/−)
Cmax (µg/ml)1.2 ± 0.051.1 ± 0.081.8 ± 0.14.7 ± 0.2
Tmax (h)
CL (ml/min per kilogram)12.311.1
Vd (l/kg)3.23.4
Half-life (h)
AUC(0→t) (h*μg/ml)4.0 ± 0.33.96 ± 0.14.27 ± 0.242.1 ± 1.2
AUC(0→∞) (h*μg/ml)
AUC-based Kpa1.010.0
AUC-based Kp,uub0.111.1
Transient steady-state Kpc1.711.6
Transient steady-state Kp,uud0.111.3
AUC based DAe9.9
Transient steady-state DAe6.9
  • a Calculated by [AUC(0–∞),brain]/[AUC(0–∞),plasma].

  • b Calculated by [AUC(0–∞),brain]/[AUC(0–∞),plasma] × [fu,brain/fu,plasma].

  • c Calculated by Cmax,brain/corresponding plasma concentration at that time (Cp,tss).

  • d Calculated by (Cmax,brain/Cp,tss) × (fu,brain/fu,plasma).

  • e DA due to the lack of efflux transporters, or Kp,knockout/Kp,wild-type or Kp,uu,knockout/Kp,uu,wild-type.