ISSN:
1432-1041
Keywords:
Key words Aprotinin
;
Arginine vasopressin; bioavailability
;
dDAVP
;
enzyme inhibitor
;
gastrointestinal tract
;
healthy volunteer
;
pharmacokinetics
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Abstract 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 μg dDAVP. For intestinal administration 500 μg 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002280050146
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