Summary
When desmopressin (DDAVP) is given to mild and moderate hemophiliacs intravenously
(i. v.) or subcutaneously (s.c.), there is a very large between-patient variability
for peak levels of factor VIII coagulant activity (VIII :C). To evaluate whether or
not between-patient variability is related to DDAVP levels achieved in plasma, we
measured drug levels in 14 hemophilic volunteers (VIII: C 2 to 31 U/dL) who were randomly
given 0.3 μg/Kg of i. v. or s. c. DDAVP and crossed-over to the other treatment after
an interval of 15–30 days. Peak DDAVP levels (Cmax) were higher for i.v. DDAVP (p <0.02), times to peak levels (tmax) were shorter for i.v. DDAVP (p <0.001). There was no difference between the i.v.
and s.c. routes for plasma DDAVP time curve (AUC) and half-life (ti/,), but there
was much larger variability for pharmacokinetic parameters with i.v. than with s.c.
DDAVP. Post-DDAVP VIII:C increased 3.4 ± 1.6 fold (i.v.) and 3.3 ±1.3 fold (s. c.)
over baseline levels, with no significant correlation between peak VIII :C and DDAVP
levels for either route of administration. These findings establish the s. c. route
of DDAVP administration to be bioequivalent in effect to the i.v. route, albeit with
less variability. At the DDAVP dosage used in this study and currently recommended
for therapy, the VIII: C response is neither a function of the rate of absorption
of the compound nor of the magnitude of its plasma concentration.
Keywords
Hemophilia - DDAVP - Vasopressin - Pharmacokinetics
