Figure 6

Brain distribution of quinidine in the rat [Westerhout J, Smeets J, Danhof M, De Lange ECM: The impact of P-gp functionality on non-steady state relationships between CSF and brain extracellular fluid. J Pharmacokin Pharmacodyn, submitted]. Average (geometric mean ±SEM) unbound quinidine concentration-time profiles following: a) 10 mg/kg, with co-administration of vehicle (-); b) 20 mg/kg, with co-administration of vehicle (-); c) 10 mg/kg with co-administration of 15 mg/kg tariquidar (+), and d) 20 mg/kg with co-administration of 15 mg/kg tariquidar (+). Black, blue, green and red symbols represent plasma, brain ECF, lateral ventricle CSF and cisterna magna CSF, respectively. Open symbols indicate data obtained without (-) and closed symbols represent data obtained with (+) the P-gp blocker tariquidar, respectively. The data show substantially lower concentrations in brain ECF (striatum) compared to lateral ventricle and cisterna magna CSF concentrations for both the 10 and 20 mg/kg dose (a, b). Upon co-administration of tariquidar, the brain ECF (striatum) concentrations were higher than those in the CSF compartments (c, d). These data show that the relationship between brain ECF and CSF concentrations is influenced by P-gp-mediated transport.