Transport of carbamazepine and drug interactions at blood-brain barrier.
OBJECTIVE
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 degree. The steady-state uptake of CBZ by rBMEC was tested for different CBZ concentrations at 37 degree. 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.


CONCLUSIONS
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.
Sun
Jing-jing
JJ
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
Xie
Lin
L
Liu
Xiao-dong
XD
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001569:Benzodiazepines / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002220:Carbamazepine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000098:blood supply*; D016572:Cyclosporine / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism; D008833:Microcirculation / Q000166:cytology; D000077152:Olanzapine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000927:Anticonvulsants; D004140:Dinitrophenols; D001569:Benzodiazepines; D002220:Carbamazepine; D016572:Cyclosporine; D000077152:Olanzapine