caa a22 4500 477056911 CHVBK 20180405111348.0 cr unu---uuuuu 170330e19960701xx s 000 0 eng 10.1007/s002280050146 doi (NATIONALLICENCE)springer-10.1007/s002280050146 Bioavailability of 1-deamino-8-D-arginine vasopressin with an enzyme inhibitor (aprotinin) from the small intestine in healthy volunteers [Elektronische Daten] [A. Fjellestad-Paulsen, L. d'Agay-Abensour, P. Höglund, J.-C. Rambaud] 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. Springer-Verlag Berlin Heidelberg, 1996 Key words Aprotinin nationallicence Arginine vasopressin nationallicence bioavailability nationallicence dDAVP nationallicence enzyme inhibitor nationallicence gastrointestinal tract nationallicence healthy volunteer nationallicence pharmacokinetics nationallicence Fjellestad-Paulsen A. Department of Clinical Pharmacology, Lund University Hospital, S-221 85 Lund, Sweden, SE aut d'Agay-Abensour L. Department of Clinical Pharmacology, Lund University Hospital, S-221 85 Lund, Sweden, SE aut Höglund P. Department of Clinical Pharmacology, Lund University Hospital, S-221 85 Lund, Sweden, SE aut Rambaud J.-C Department of Clinical Pharmacology, Lund University Hospital, S-221 85 Lund, Sweden, SE aut https://doi.org/10.1007/s002280050146 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050146 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fjellestad-Paulsen A. Department of Clinical Pharmacology, Lund University Hospital, S-221 85 Lund, Sweden, SE aut NATIONALLICENCE 700 1- d'Agay-Abensour L. Department of Clinical Pharmacology, Lund University Hospital, S-221 85 Lund, Sweden, SE aut NATIONALLICENCE 700 1- Höglund P. Department of Clinical Pharmacology, Lund University Hospital, S-221 85 Lund, Sweden, SE aut NATIONALLICENCE 700 1- Rambaud J.-C Department of Clinical Pharmacology, Lund University Hospital, S-221 85 Lund, Sweden, SE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer