Stereoselective Transport of Baclofen Across the Blood–Brain Barrier in Rats as Determined by the Unit Impulse Response Methodology

The blood–brain barrier transport characteristics of racemic baclofen and the separate R- and S-enantiomers have been determined in vivo in rats by using the unit impulse response methodology. Transport rate was determined as blood–brain barrier clearance, the volume of plasma per unit time cleared of baclofen by transport across the blood–brain barrier. Plasma elimination kinetics and CSF elimination kinetics did not differ among racemic baclofen and the R-and S-enantiomers. Transport of each compound could be described by a linear V(t] curve, suggesting the absence of saturable transport processes in the concentration range studied. However, for R-baclofen the blood–brain barrier clearance (4.7 ± 1.0 µl/min, mean ± SE; n = 6) and cumulative transported amount (0.085 ± 0.007%; n = 6) were significantly higher than these values for the S-enantiomer (1.1 ± 0.3 µl/min, 0.031 ± 0.005%; n = 6) and racemic baclofen (1.0 ± 0.1 µl/min, 0.036 ± 0.003%; n = 6). These findings indicate that there is stereoselective transport of baclofen across the blood–brain barrier.