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Acta Pharmacologica Sinica 2006 February; 27 (2): 249-253; doi: 10.1111/j.1745-7254.2006.00246.x |
| Original Article | [ Full text ] |
| Transport of carbamazepine and drug interactions at blood-brain barrier1 |
Jing-jing SUN, Lin XIE, Xiao-dong LIU2 Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China |
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Aim: To investigate the characteristics of carbamazepine (CBZ) transport and drug interactions at the blood-brain barrier.
Methods: Cultured rat brain microvascular endothelial cells (rBMEC) were used as an in vitro model of the blood-brain barrier (BBB). When cells became confluent, CBZ uptake over time was recorded by incubation of the cells in a medium containing 10 mg/L CBZ at 37 ºC. The steady-state uptake of CBZ by rBMEC was tested for different CBZ concentrations at 37 ºC. The effects of various agents on the steady-state uptake of CBZ and efflux of CBZ from rBMEC were also studied.
Results: The uptake of CBZ by rBMEC was time- and concentration-dependent. The steady-state uptake occurred at 30 min for incubation. The steady-state uptake was significantly increased (P<0.01) by treatment with dinitrophenol. The co-administration of cyclosporine A significantly increased the steady-state uptake of CBZ by the rBMEC, whereas co-administration of olanzapine significantly decreased the uptake in a concentration- and temperature-dependent manner. The efflux of CBZ from rBMEC was inhibited by CsA.
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Keywords: carbamazepine; blood-brain barrier; cyclo-sporine A; olanzapine; rat brain micro-vascular endothelial cells; drug interaction |
1 Project supported by the National High Technology Research and Development Program of China (863 Program, No 2003AA2Z347A). |
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[ Full text ] |
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