Correlation between quinolone uptakes by BCECs in vitro and brain-to-plasma concentration ratios in rats.
Transport of 11 quinolones at the blood-brain barrier (BBB) was studied in vitro by using primarily cultured rat brain capillary endothelial cells (BCECs) and in vivo brain-to-plasma concentration ratios. In vitro, when cells reached confluence, a time course of quinolone uptake was recorded by incubation with a medium contraining quinolones 20 microg/ml at 37 degrees C. A simple two-compartment model was used for fitting the uptake time course and corresponding uptake parameters were estimated. In vivo rats were anesthetized, after in 10 mg/kg of quinoloes followed by infusion of 4 mg/kg/h for 2 hours, the drug concentrations in plasma and brain were measure and brain-to-plasma concentration ratios were calculated. Result showed that sparfloxacin and prulifloxacin have higher uptakes by BCECs and brain-to-plasma concentration ratios, compared with other quinolones, which indicated that the two drugs more easily penetrate into BBB. A good correlation between uptakes by BCECs and brain-to-plasma concentration ratios was found. These results demonstrated uptakes by BCECs in vitro might give prediction of brain-to-plasma ratio for quinolones.
Liu
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XD
Centre of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
Wang
D W
DW
Xie
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L
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D042783:Endothelial Cells / Q000378:metabolism*; D024841:Fluoroquinolones / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D024841:Fluoroquinolones