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 microliters/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 microliters/min, 0.031 +/- 0.005%; n = 6) and racemic baclofen (1.0 +/- 0.1 microliters/min, 0.036 +/- 0.003%; n = 6). These findings indicate that there is stereoselective transport of baclofen across the blood-brain barrier.
van Bree
J B
JB
Center for Bio-Pharmaceutical Sciences, University of Leiden, The Netherlands.
Heijligers-Feijen
C D
CD
de Boer
A G
AG
Danhof
M
M
Breimer
D D
DD
D000818:Animals; D001418:Baclofen / Q000493:pharmacokinetics*; D001692:Biological Transport; D001812:Blood-Brain Barrier; D008657:Metabolic Clearance Rate; D051381:Rats; D013237:Stereoisomerism
D001418:Baclofen