Desmopressin as a pharmacological tool in vasopressinergic hypothalamus-pituitary-adrenal axis modulation: neuroendocrine, cardiovascular and coagulatory effects.
Arginine-vasopressin (AVP) is a physiological co-activator of the hypothalamus-pituitary-adrenal (HPA) axis, together with corticotrophin releasing hormone (CRH). A synthetic analogue of AVP, desmopressin (dDAVP), is often used as a pharmacological tool to assess co-activation in health and disease. The relation between dDAVP's neuroendocrine, cardiovascular, pro-coagulatory, anti-diuretic and non-specific stress effects has not been studied. A randomized, double-blind, placebo-controlled, three-way crossover study was performed in 12 healthy male and female volunteers (6 : 6). dDAVP was administered intravenously as a 10 μg bolus (over 1 min) or a 30 μg incremental infusion (over 60 min). Neuroendocrine, cardiovascular, pro-coagulatory, anti-diuretic effects and adverse events (AEs) were recorded, and autonomic nervous system (ANS) activation evaluated. The incremental infusion reached 1.8-fold higher dDAVP concentrations than the bolus. Neuroendocrine effects were similar for the 10 μg dDAVP bolus and the 30 μg incremental infusion, while cardiovascular and coagulatory effects were greater with the 30 µg dose. Osmolality and ANS activity remained uninfluenced. AEs corresponded to dDAVP's side-effect profile. In conclusion, the neuroendocrine effects of a 10 μg dDAVP bolus administered over 1 min are similar to those of a 30 μg incremental infusion administered over one hour, despite higher dDAVP concentrations after the infusion. Cardiovascular and coagulatory effects showed clear dose-related responses. A 10 μg dDAVP bolus is considered a safe vasopressinergic function test at which no confounding effects of systemic or autonomic stress were seen.
Centre for Human Drug Research, Leiden, The Netherlands.
G E
GE
Jacobs
E G J
EG
Hulskotte
J M A
JM
van Gerven
L
L
Zuurman
M L
ML
de Kam
J
J
Elassaiss-Schaap
G
G
Ruigt
J
J
van Pelt
B W M M
BW
Peeters
P A M
PA
Peeters
J
J
Burggraaf
D000293:Adolescent; D000328:Adult; D050034:Antidiuretic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects; D018592:Cross-Over Studies; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D055815:Young Adult
D050034:Antidiuretic Agents; D003894:Deamino Arginine Vasopressin