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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.