In-vitro evidence for carrier-mediated uptake of acidic drugs by isolated bovine brain capillaries.
[3H]Acetic acid was taken up into the isolated brain capillaries in a temperature and concentration dependent manner. The initial uptake rates were pH dependent over the range 5.0-7.4. An increase of the uptake rate with decrease in medium pH was not seen in the presence of unlabelled acetic acid (10 mM). The uptake of [3H]acetic acid was significantly reduced in the presence of several drugs having a monocarboxylic group. The initial uptake of [14C]salicylic acid was also pH dependent and was inhibited by acetic acid and acidic drugs. A mutually competitive inhibition was observed for the uptake of acetic acid and salicylic acid. The present study demonstrates that acidic drugs having a monocarboxylic group are transported by a common carrier-mediated system into the brain capillaries.
Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
T
T
Terasaki
Y S
YS
Kang
T
T
Ohnishi
A
A
Tsuji
D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D000818:Animals; D001812:Blood-Brain Barrier; D001923:Brain Chemistry; D002196:Capillaries / Q000378:metabolism*; D002417:Cattle; D002560:Cerebrovascular Circulation / Q000502:physiology; D004337:Drug Carriers; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012459:Salicylates / Q000378:metabolism; D020156:Salicylic Acid; D013696:Temperature
D000085:Acetates; D004337:Drug Carriers; D004364:Pharmaceutical Preparations; D012459:Salicylates; D020156:Salicylic Acid; D019342:Acetic Acid