Pharmacokinetics of 1-deamino-8-d-arginine vasopressin after various routes of administration in healthy volunteers

Summary 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 μg of dDAVP. The intranasal and sublingual doses were 20 μg and the rectal dose was 50 μ. Oral administration of dDAVP was effected with a 200‐μg 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 (t) 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.