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. DESIGN 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 mug of dDAVP. The intranasal and sublingual doses were 20 mug and the rectal dose was 50 mug. Oral administration of dDAVP was effected with a 200-mug tablet. MEASUREMENTS 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 dDVAP 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. CONCLUSION The bioavailability of dDAVP seems lower than previously reported after intranasal and oral administration.