A pharmacokinetic and pharmacodynamic comparison of desmopressin administered as whole, chewed and crushed tablets, and as an oral solution

Purpose: We performed a crossover study to determine the relative pharmacok inetic bioavailability and antidiuretic activity of desmopressin in 16 oral ly hydrated, healthy human subjects. Materials and Methods: The investigation included 5 study periods with 1 pe riod used to establish baseline diuresis in the absence of desmopressin and the remaining 4 randomized to a ingle 0.6 mg. oral dose of desmopressin ad ministered as whole, crushed or chewed tablets, or as an oral solution. Ser ial plasma samples were collected for 12 hours for desmopressin pharmacokin etic analysis. Pharmacodynamics were assessed by measuring changes in urine volume and osmolality from baseline. Standard bioequivalence metrics were used to compare the pharmacokinetics and pharmacodynamics of crushed and ch ewed tablets, and oral solution to that of swallowing whole tablets, Results: The 90% confidence interval analysis of log transformed plasma des mopressin area under the plasma concentration-time curve from time 0 to inf inity and maximum plasma drug concentration showed that crushed and chewed tablet treatments were bioequivalent to swallowing whole tablets. The 90% c onfidence interval analysis for the decrease in urine volume and increase i n urine osmolality demonstrated that crushed and chewed tablets, and oral s olution treatments were equivalent to whole tablet treatment in the area un der curve from time 0 to the last sampling time point, and maximum drug eff ect. Conclusions: The results of this study imply that desmopressin administered orally as crushed or chewed tablets, or as an oral solution has the same n et effect on decreasing urine volume and increasing urine osmolality as swa llowing tablets whole.