Intestinal absorption of the quaternary trospium chloride: Permeability-lowering factors and bioavailabilities for oral dosage forms

The intestinal absorption mechanism, permeability and bioavailability of the parasympatholytic trospium chloride has been investigated in vitro and in vivo in rats, in order to gain abetter mechanistic explanation for the underlying cause leading to low bioavailability of quaternary compounds following peroral dosing. Permeability determinations were done in Ussing-type chambers with rat jejunum and human Caco-2 cells. In vivo bioavailability and mass balance studies were done in rats. Absorption was studied from trospium chloride solutions in saline and from w/o microemulsions and cyclodextrin complex formulations. The absorption mechanism of trospium chloride across the intestinal epithelium is rather complex and involves P-glycoprotein-mediated secretion and saturable binding to intestinal mucus. Trospium permeability across the intestinal epithelium increases nonlinearly with rising drug concentrations at the apical membrane. Neither the microemulsions nor the cyclodextrin formulations increased the permeability of trospium in vitro, leading to lower or equal bioavailability of these formulations in vivo as compared with the aqueous solution control. (C) 1997 Elsevier Science B.V.