Simultaneous microdialysis in brain and blood of the mouse: extracellular and intracellular brain colchicine disposition.
A simultaneous brain and blood microdialysis system was developed to study the passage of colchicine through the blood-brain barrier in the mouse. Colchicine was administered as a bolus in the jugular vein (1.5 mg kg-1) and its hippocampal extracellular fluid (ECF) and blood kinetics were determined over a 4 h period using two microdialysis probes, one in the dorsal hippocampus, the other in the inferior vena cava. Colchicine rapidly diffused into the hippocampus (maximum concentration in the first dialysate sample) and brain and blood concentrations declined in parallel, suggesting rapid equilibration between these two compartments. However, only 6. 7% of total blood colchicine, 14% of unbound colchicine was present in the hippocampus suggesting that the P-glycoprotein efflux pump limits colchicine uptake by the brain. We also found, using conventional tissue homogenate analysis in parallel, that the concentration of colchicine in the hippocampal ECF was 10 times less than that in the intracellular space and that the hippocampus colchicine concentration was 2.8 times higher than that of the rest of the brain. This study shows that the simultaneous brain and blood microdialysis can be used to measure the passage of colchicine through the blood-brain barrier and to estimate the brain extra- and intracellular distribution of colchicine.
Evrard
P A
PA
Pharmacokinetics Laboratory/FATC 7355, School of Pharmacy, Catholic University of Louvain, 1200 Brussels, Belgium.
Ragusi
C
C
Boschi
G
G
Verbeeck
R K
RK
Scherrmann
J M
JM
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003078:Colchicine / Q000097:blood / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017551:Microdialysis; D009994:Osmolar Concentration; D013997:Time Factors
D003078:Colchicine