The duration of antidiuretic response of two desmopressin nasal sprays.
The duration of antidiuretic response and pharmacokinetics of desmopressin were investigated in 16 healthy, male overhydrated volunteers after intranasal administration of 20 microg desmopressin (dDAVP). The antidiuretic activity was determined by measuring urine osmolality and diuresis over a period of 24 hours. Both study preparations were equally effective regarding a rapid onset of activity and a highly reproducible extent of effect. Urine osmolalities, analyzed as areas under the time curve (AUCosm) were similar for both nasal sprays. Urine volumes were comparable. Bioequivalence was assessed for the primary criterion AUCosm by a calculated mean ratio (test/reference) of 100.9% (90% confidence interval ranging from 88.0% to 115.6%). Plasma levels of desmopressin, measured by a specific and sensitive radioimmunoassay method, were already detectable 20 minutes after administration. The mean time courses showed a similar shape with increased concentration levels for the test preparation. Consequently maximum desmopressin plasma concentrations were different, showing high interindividual variability. However, the times of reaching maximum plasma concentrations were similar. AUC(0-24h) was significantly raised after treatment with the test preparation (mean ratio of 127.9%; 90% confidence interval ranging from 106.6% to 153.5%). A subanalysis of the 2 reference batches with the two-sided t-test procedure for parallel groups resulted in a mean ratio of 83.1% with a 90% confidence interval ranging from 67.2% to 102.7%. The estimated ratios of the 2 batches of the reference preparation were borderline to the equivalence range. In conclusion, both study preparations had the same pronounced biological effect with different desmopressin bioavailabilities.
Medical Department, Gebro Broschek GmbH, Fieberbrunn, Austria.
N
N
Eller
C J
CJ
Kollenz
P
P
Bauer
G
G
Hitzenberger
D000281:Administration, Intranasal; D000328:Adult; D018592:Cross-Over Studies; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006490:Hemostatics / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D008297:Male; D009994:Osmolar Concentration; D014563:Urodynamics / Q000187:drug effects
D006490:Hemostatics; D003894:Deamino Arginine Vasopressin