D Argenti1, D Ireland, D L Heald. 1. Aventis Pharmaceuticals, U.S. Medical Affairs-Clinical Pharmacology and Pharmacokinetics, Parsippany, New Jersey 08807, USA.
Abstract
PURPOSE: We performed a crossover study to determine the relative pharmacokinetic bioavailability and antidiuretic activity of desmopressin in 16 orally hydrated, healthy human subjects. MATERIALS AND METHODS: The investigation included 5 study periods with 1 period used to establish baseline diuresis in the absence of desmopressin and the remaining 4 randomized to a single 0.6 mg. oral dose of desmopressin administered as whole, crushed or chewed tablets, or as an oral solution. Serial plasma samples were collected for 12 hours for desmopressin pharmacokinetic 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 chewed tablets, and oral solution to that of swallowing whole tablets. RESULTS: The 90% confidence interval analysis of log transformed plasma desmopressin area under the plasma concentration-time curve from time 0 to infinity and maximum plasma drug concentration showed that crushed and chewed tablet treatments were bioequivalent to swallowing whole tablets. The 90% confidence interval analysis for the decrease in urine volume and increase in urine osmolality demonstrated that crushed and chewed tablets, and oral solution treatments were equivalent to whole tablet treatment in the area under curve from time 0 to the last sampling time point and maximum drug effect. CONCLUSIONS: The results of this study imply that desmopressin administered orally as crushed or chewed tablets, or as an oral solution has the same net effect on decreasing urine volume and increasing urine osmolality as swallowing tablets whole.
RCT Entities:
PURPOSE: We performed a crossover study to determine the relative pharmacokinetic bioavailability and antidiuretic activity of desmopressin in 16 orally hydrated, healthy human subjects. MATERIALS AND METHODS: The investigation included 5 study periods with 1 period used to establish baseline diuresis in the absence of desmopressin and the remaining 4 randomized to a single 0.6 mg. oral dose of desmopressin administered as whole, crushed or chewed tablets, or as an oral solution. Serial plasma samples were collected for 12 hours for desmopressin pharmacokinetic 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 chewed tablets, and oral solution to that of swallowing whole tablets. RESULTS: The 90% confidence interval analysis of log transformed plasma desmopressin area under the plasma concentration-time curve from time 0 to infinity and maximum plasma drug concentration showed that crushed and chewed tablet treatments were bioequivalent to swallowing whole tablets. The 90% confidence interval analysis for the decrease in urine volume and increase in urine osmolality demonstrated that crushed and chewed tablets, and oral solution treatments were equivalent to whole tablet treatment in the area under curve from time 0 to the last sampling time point and maximum drug effect. CONCLUSIONS: The results of this study imply that desmopressin administered orally as crushed or chewed tablets, or as an oral solution has the same net effect on decreasing urine volume and increasing urine osmolality as swallowing tablets whole.
Authors: R Court; M T Chirehwa; L Wiesner; N de Vries; J Harding; T Gumbo; G Maartens; H McIlleron Journal: Int J Tuberc Lung Dis Date: 2019-10-01 Impact factor: 2.373