BIOAVAILABILITY OF 1-DEAMINO-8-D-ARGININE VASOPRESSIN WITH AN ENZYME-INHIBITOR (APROTININ) FROM THE SMALL-INTESTINE IN HEALTHY-VOLUNTEERS

Objective: The bioavailability of an aqueous solution of 1-deamino-S-D -arginine vasopressin (dDAVP), with and without an enzyme inhibitor, w as studied in six healthy, male volunteers aged 19-34 years, followed for 8 h after each drug administration, Methods: For i.v. administrati on the subjects received 4 mu g dDAVP. For intestinal administration 5 00 mu g dDAVP was administered directly in two separate sessions, in t he first part of the duodenum via a triple-lumen channel tube. In one session a solution of isotonic polyethylene glycol (PEG) was given as a continuous enteral perfusion. In the other session a solution of PEG and aprotinin was administered enterally at the constant rate of 5 ml . min(-1) for 4 h. Plasma dDAVP was measured using a specific, sensit ive radioimmunoassay and intestinal juice was collected for measuremen t of lipase, chymotrypsin and pH every 30 min for 5 h. Results: The in testinal chymotrypsin activity was decreased after perfusion of aproti nin while the lipase activity was not modified. After i.v. administrat ion, the half-life of elimination of dDAVP was 1.56 h and plasma clear ance 1.24 ml . min . kg(-1). The mean bioavailability after duodenal a dministration of dDAVP + aprotinin was 0.46% compared with 0.09% after duodenal administration of dDAVP alone. The bioavailability of dDAVP after direct duodenal administration of an aqueous solution was simila r to that after swallowing a tablet in a previous study and increased 5 times when given together with a perfusion of an enzyme inhibitor.