Physical model approach to gastrointestinal absorption of prostaglandins III: In situ rat intestinal absorption of dinoprostone.

In situ absorption studies with dinoprostone in the rat jejunum were carried out to provide a quantitative mechanistic insight of the absorption process. The variables included buffer pH (3.5-9.5), buffer capacity, hydro-dynamics in the lumen, and concentration. The disappearance kinetics from the lumen was first order. The rate decreased with increasing pH in a sigmoidal manner and reached a minimum at about pH 9. These results indicate the effects of the partitioning of nondissociated species in the lipoidal membrane and transport across aqueous pores. The rate was higher with the higher degree of agitation of the lumenal solution. Between two hydrodynamic situations, the differences in the rates were large at pH 4.5 where the transport was largely aqueous diffusion controlled and then tended to become smaller with increasing pH where the transport became effectively membrane controlled. The 15-oxo- and 13,14-dihydro-15-oxo metabolites of dinoprostone were found. The physical model was applied to quantify the permeability coefficients of the aqueous diffusion layer and the aqueous pores of the membrane and the effective membrane transport-bioconversion permeability coefficient at various pH values. The overall absorption dinoprostone was similar to that of the less lipophilic dinoprost reported earlier and also more rapid. Hence, baseline absorption studies were completed with two major reference prostaglandins from which estimations of intestinal absorption can be made for their analogues and derivatives.