The aim of this work was to investigate the efficiency of transporting
the orally inactive renin inhibitor A-64662 through oral mucosa-floor
of mouth, cheek, or gum-using the dog as an animal model. It has been
demonstrated that A-64662, can be effectively delivered to the bloods
tream through mouth mucosa with various dosage forms. Compared to bucc
al adsorption, a relatively fast onset was observed after sublingual a
dministration of an aqueous solution. A slightly higher bioavailabilit
y but lower C-max and extended plasma drug levels were observed after
sublingual administration of a slow-release gel formulation. This work
has also shown that mucoadhesive patch application can provide sustai
ned and controlled release of A-64662 by either buccal or gum administ
ration. The absorption through the gum is slower than the cheek.