Abstract
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 °C. The steady-state uptake of CBZ by rBMEC was tested for different CBZ concentrations at 37 °C. 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.
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Project supported by the National High Technology Research and Development Program of China (863 Program, No 2003AA2Z347A).
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Sun, Jj., Xie, L. & Liu, Xd. Transport of carbamazepine and drug interactions at blood-brain barrier. Acta Pharmacol Sin 27, 249–253 (2006). https://doi.org/10.1111/j.1745-7254.2006.00246.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00246.x
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