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Increased drug delivery to the brain by P‐glycoprotein inhibition

Although the antidiarrheal loperamide is a potent opiate, it does not produce opioid central nervous system effects at usual doses in patients. On the basis of in vitro studies demonstrating that loperamide is a substrate for the adenosine triphosphate–dependent efflux membrane transporter P‐glycoprotein, we postulated that inhibition of P‐glycoprotein with quinidine would increase entry of loperamide into the central nervous system with resultant respiratory depression.