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-8-D-arginine vasopressin (dDAVP), with and without an enzyme inhibitor, was studied in six healthy, male volunteers aged 19-34 years, followed for 8 h after each drug administration.


METHODS
For i.v. administration the subjects received 4 micrograms dDAVP. For intestinal administration 500 micrograms dDAVP was administered directly, in two separate sessions, in the 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, sensitive radioimmunoassay and intestinal juice was collected for measurement of lipase, chymotrypsin and pH every 30 min for 5 h.


RESULTS
The intestinal chymotrypsin activity was decreased after perfusion of aprotinin while the lipase activity was not modified. After i.v. administration, the half-life of elimination of dDAVP was 1.56 h and plasma clearance 1.24 ml.min.kg-1. The mean bioavailability after duodenal administration 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 similar to that after swallowing a tablet in a previous study and increased 5 times when given together with a perfusion of an enzyme inhibitor.
Fjellestad-Paulsen
A
A
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
d'Agay-Abensour
L
L
Höglund
P
P
Rambaud
J C
JC
D000328:Adult; D007611:Aprotinin / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D003894:Deamino Arginine Vasopressin / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004386:Duodenum / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D008297:Male; D015842:Serine Proteinase Inhibitors / Q000493:pharmacokinetics*; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; D007611:Aprotinin; D002918:Chymotrypsin; D003894:Deamino Arginine Vasopressin