Pharmacokinetics of 1-deamino-8-D-arginine vasopressin after various routes of administration in healthy volunteers.
OBJECTIVE
We investigated the pharmacokinetics and biological effects of 1-deamino-8-D-arginine vasopressin (dDAVP) in healthy adults after intravenous, subcutaneous, intranasal, peroral, sublingual and intrarectal administration.


METHODS
Eight normal volunteers were studied over an 8-hour period after each drug administration, separated by at least one week. For intravenous and subcutaneous administration, the subjects received 2 micrograms of dDAVP. The intranasal and sublingual doses were 20 micrograms and the rectal dose was 50 micrograms. Oral administration of dDAVP was effected with a 200-micrograms tablet.


METHODS
Plasma and urinary levels of dDAVP were measured using a specific and sensitive radioimmunoassay.


RESULTS
A significant increase of urine osmolality was observed after all routes of administration, except the sublingual and intrarectal for up to 8 hours after administration. After intravenous administration, the half-life of elimination (t1/2) of dDAVP was 78 +/- 10 minutes. An extensive adsorption of dDAVP to the plastic syringe was found with intravenous but not with subcutaneous administration. Using the area under the curve of dDAVP from the subcutaneous administration as a reference, bioavailability was found to be 3.4% after intranasal administration and 0.1% after oral administration. After sublingual and intrarectal routes of administration no detectable dDAVP was found in the blood; however, low amounts were found in the total 24-hour urine.


CONCLUSIONS
The bioavailability of dDAVP seems lower than previously reported after intranasal and oral administration.
Fjellestad-Paulsen
A
A
Department of Clinical Pharmacology, Lund University Hospital, University of Lund, Sweden.
Höglund
P
P
Lundin
S
S
Paulsen
O
O
D000281:Administration, Intranasal; D000284:Administration, Oral; D000285:Administration, Rectal; D000286:Administration, Sublingual; D000328:Adult; D001682:Biological Availability; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration
C025161:vasopressin, deamino-homo-Arg-; D003894:Deamino Arginine Vasopressin