Intranasal and intravenous administration of desmopressin: effect on F VIII/vWF, pharmacokinetics and reproducibility.
A comparison was made of intranasal administration of 300 micrograms desmopressin (DDAVP) by spray, with intravenous administration of 0.2, 0.3 and 0.4 microgram DDAVP/kg in 10 healthy volunteers. The effect of DDAVP was measured on F VIII/vWF complex and on plasminogen activator release. In addition, plasma levels of DDAVP were determined using a specific and sensitive radioimmunoassay. Moreover, the reproducibility of the spray effect in 10 healthy volunteers was tested after administration of 300 micrograms DDAVP intranasally by spray on 5 different occasions. Plasma levels of DDAVP showed a clear dose-response with the maximum levels at 0.4 microgram/kg i.v. The effect of the spray approximated the 0.2 microgram/kg response. However, the maximum response in both F VIII/vWF complex and plasminogen activator release was obtained after 0.3 microgram/kg i.v. The response to 0.4 microgram/kg i.v. was not significantly different from the response to 0.3 microgram/kg indicating that maximum stimulation was reached with 0.3 micrograms/kg. There was no correlation between plasma levels of F VIII/vWF and DDAVP indicating that the biological response to DDAVP is subjected to saturation kinetics. The reproducibility of the effect of the spray dose on VIII:C was 21% (c.v.) and 27% for the intra-individual and inter-individual variation, respectively, and compared favorably with intravenous administration. Intranasal DDAVP (300 micrograms) is as effective as 0.2 micrograms/kg intravenously and provides an accurate, reproducible and convenient alternative to parenteral administration.
D000281:Administration, Intranasal; D000328:Adult; D000941:Antigens / Q000032:analysis; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D005169:Factor VIII / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D014841:von Willebrand Factor / Q000378:metabolism*
D000941:Antigens; C029417:Von Willebrand antigen; D014841:von Willebrand Factor; D005169:Factor VIII; D003894:Deamino Arginine Vasopressin