Acidic drug transport in vivo through the blood-brain barrier. A role of the transport carrier for monocarboxylic acids.
The relationship of the transports between acidic drugs and monocarboxylic acids through the blood-brain barrier (BBB) was examined using the carotid artery injection technique in rats. The BBB uptakes of [3H]acetic acid and [14C]salicylic acid were significantly reduced by the presence of the respective unlabeled compounds, valproic acid, lactic acid, benzoic acid, nicotinic acid or beta-lactam antibiotics (benzylpenicillin, propicillin and cefazolin), but was not reduced by choline, phenylalanine and a basic drug, eperisone. A remarkable pH dependency was observed for the BBB uptake of [14C]salicylic acid at the pH region of 4.0 to 7.4. Interestingly, 10 mM of salicylic acid diminished significantly the pH dependent BBB uptake of [14C]salicylic acid. Similar results were obtained in the BBB uptake of [14C]nicotinic acid. No significant difference was observed in the transport of monocarboxylic acids through the BBB between normotensive Wistar KY rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). From these observations, acidic drugs could be transported by a carrier-mediated system for monocarboxylic acids at the BBB and the transport system was not changed by the disease state.
Kang
Y S
YS
Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Terasaki
T
T
Tsuji
A
A
D000085:Acetates / Q000493:pharmacokinetics*; D019342:Acetic Acid; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000502:physiology*; D001923:Brain Chemistry; D002339:Carotid Arteries; D002794:Choline / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007269:Injections, Intra-Arterial; D007769:Lactams; D009539:Nicotinic Acids / Q000493:pharmacokinetics*; D010276:Parasympatholytics / Q000494:pharmacology; D010649:Phenylalanine / Q000494:pharmacology; D011427:Propiophenones / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D012459:Salicylates / Q000493:pharmacokinetics*; D020156:Salicylic Acid; D014316:Tritium; D014635:Valproic Acid / Q000494:pharmacology
D000085:Acetates; D000900:Anti-Bacterial Agents; D007769:Lactams; D009539:Nicotinic Acids; D010276:Parasympatholytics; D011427:Propiophenones; D012459:Salicylates; D014316:Tritium; C030848:eperisone; D010649:Phenylalanine; D014635:Valproic Acid; D002794:Choline; D020156:Salicylic Acid; D019342:Acetic Acid