Delivery of acetaminophen to the central nervous system and the pharmacological effect after intranasal administration with a mucoadhesive agent and absorption enhancer.

Acetaminophen, a central antipyretic and analgesic drug, is one of the most commonly used drugs among individuals of all ages throughout the world. This study pharmacokinetically and pharmacodynamically investigated the transport of acetaminophen to the central nervous system and systemic circulation after intranasal (i.n.) administration, and evaluated the potential of a transnasal acetaminophen formulation in comparison to other routes of administration. Direct transport to the brain and the pharmacological effect after the i.n. administration of acetaminophen with polyvinylpyrrolidone (PVP; a mucoadhesive agent) and poly-l-arginine (PLA; an absorption enhancer) were investigated to improve retention of the dosage solution in the olfactory epithelium region and enhance the transfer of acetaminophen to the brain. The transport of acetaminophen to the brain was rapid, and the concentration in the brain, especially the olfactory bulb, was higher after i.n. administration, resulting in a greater antipyretic effect in comparison to other routes of administration. The delivery system using PVP and PLA produced a high and prolonged antipyretic effect by enhancing the transfer of acetaminophen to the brain through suppression of the transfer to systemic circulation. Thus, this transnasal drug delivery system using PVP and PLA may be a promising method for transporting acetaminophen to the brain.