The Intranasal Absorption of the Quaternary Ammonium Compounds Neostigmine Bromide and Tubocurarine Chloride in the Rat

Abstract

The systemic absorptions of the quaternary ammonium compounds, neostigmine bromide and (+)-tubocurarine chloride, from the nasal cavity were compared in the adult male rat with those obtained by the oral and intravenous routes. By the oral route, neostigmine bromide was absorbed to a limited extent and tubocurarine chloride demonstrated undetectable plasma levels. In contrast, use of the intranasal route resulted in plasma drug levels that were either significantly higher or readily detectable. Greater systemic absorptions and, thereby, improved bioavailabilities were achieved by coadministering the title drugs with sodium glycocholate, a surfactant, or with amastatin, an aminopeptidase inhibitor. For both drugs, bioavailabilities in the presence of amastatin were greater than in the presence of sodium glycocholate (≥90% vs. ≥70%). Differences in the rate and extent of absorption of the quaternary ammonium compounds across the nasal mucosa appeared to reflect differences in molecular weight.