The pharmacokinetics and pharmacodynamics of desmopressin: effect on plasma factor VIII:C and von Willebrand factor.
The relationship between plasma concentrations of desmopressin and clotting factors Factor VIII:C (FVIII:C) and von Willebrand Factor (vWF) were explored after a single 15-minute intravenous infusion of desmopressin (0.3 microg/kg) to 28 healthy male subjects. Individual plasma desmopressin-vWF and desmopressin-FVIII:C concentration/response-time data were fitted to a pharmacodynamic sigmoid E ( max ) model linked to a two-compartment open pharmacokinetic model (Ke0 link). The model demonstrated that the onset rate of pharmacodynamic activity for FVIII:C and vWF was relatively rapid following intravenous administration. However, the offset rate of pharmacodynamic activity was rate-limited by the elimination rate of desmopressin. Mean maximum pharmacodynamic activity for both factors was estimated to be three- to four-times higher than baseline activity, and the mean desmopressin concentrations that produce half-maximal effects were approximately 250 to 300 pg/mL. Interindividual variation in pharmacodynamic-parameter estimates were of the magnitude that suggests a wide range of pharmacodynamic responses are possible for a fixed desmopressin dose.
Argenti
D
D
Rhône-Poulenc Rorer, Collegeville, PA 19426, USA.
Jensen
B K
BK
Heald
D
D
D000293:Adolescent; D000328:Adult; D000465:Algorithms; D003894:Deamino Arginine Vasopressin / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005169:Factor VIII / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D017711:Nonlinear Dynamics; D014841:von Willebrand Factor / Q000378:metabolism*
D007004:Hypoglycemic Agents; D014841:von Willebrand Factor; D005169:Factor VIII; D003894:Deamino Arginine Vasopressin