Reported studies dealing with the clinical use of DDAVP in mild and moderate hemophilia A patients show a very large between-patient variability for the maximum increase of VIII:C after the drug given intravenously (i.v.) or subcutaneously (s.c.). By measuring DDAVP plasma levels with a sensitive and specific RIA method, we elected to evaluate whether or not between-patient response variability was related to the variability of DDAVP levels achieved in their plasma. To this purpose 14 moderate

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... r mild hemophilic volunteers (baseline VIII : C 4 to 31 U/dL) were randomly given 0.3 pg/Kg of i.v. or s.c. DDAVP with a between-treatment interval of 15 - 30 days. Plasma DDAVP pharmacokinetics in relation to the routes of administration are shown in the table.Pack levels (Cmax) were higher after i.v. DDAVP (p < 0.02). Time to peak levels (tmax) was shorter for i.v. DDAVP (p < 0.001). There was no difference between i.v. and s.c. DDAVP for plasma time curve (AUC) and half-life (t½).The bioavailability of the s.c. route relative to the i.v. route was 85 ° 32%. Of further interest, was the greater variability of the i.v. pharmacokinetics compared to the s.c. data. These differences were reflected in the VIII:C response. Maximum VIII:C increase over baseline levels was 3.2 ° 2.4 fold (i.v.) and 3.2 ° 1.3 fold (s.c.) (n.s.).Thus the i.v. route gave a marginally greater response but the effect was more variable than the s.c. route. Finally, no significant correlation was found between the VIII:C response and plasma DDAVP levels for either route of administration (i.v. route r = 0.03, s.c. route r = 0.23).These findings establish the subcutaneous route to be bioequivalent in effect to the intravenous route with less variation. This study also demonstrates that the VIII:C response to DDAVP is neither a function of the rate of absorption of the corrpound into the body nor the magnitude of the plasma concentration.