European Journal of Drug Metabolism and Pharmacokinetics 2012-12-01

Permeation and metabolism of cocaine in the nasal mucosa.

Hefei Zhang, Thomas E Prisinzano, Maureen D Donovan

Index: Eur. J. Drug Metab. Pharmacokinet. 37(4) , 255-62, (2012)

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Abstract

The rapid onset of psychostimulatory effects of cocaine following intranasal administration suggests either extremely rapid absorption into the bloodstream or the potential for cocaine's access to the suggested direct nose-to-brain transport pathway. Cocaine transport was measured across excised bovine olfactory and respiratory mucosa to investigate site-specific uptake of cocaine. Flux in both the mucosal-to-submucosal (J (m-s)) and submucosal-to-mucosal (J (s-m)) directions across normal, 2, 4-dinitrophenol (2, 4-DNP) exposed, and de-epithelialized tissues increased linearly with increasing cocaine concentration, and no significant differences (p < 0.05) in directional permeability were observed for each condition. Some metabolism of cocaine to benzoylecgonine was observed, both in full-thickness and de-epithelialized tissues, demonstrating the activity of the submucosal tissues, in addition to the epithelial cell layer, in determining the disposition of cocaine. Results indicate that cocaine is transported across the nasal mucosa predominantly via passive diffusion, and no significant differences were observed between transport behaviors in the olfactory and nasal respiratory tissues.