Acta Pharmacologica Sinica 2006 February; 27 (2): 249-253; doi: 10.1111/j.1745-7254.2006.00246.x

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.

Conclusion: The transport of CBZ at the BBB is mediated by many transporters. Some specific ABC (ATP-binding cassette, ABC ) efflux transporters may be involved in the transport of CBZ. Drugs influence the transport of CBZ at the BBB in different ways.

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).