Transport of carbamazepine and drug interactions at blood-brain barrier
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 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:
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.