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Effect of food intake on the pharmacokinetics and antidiuretic activity of oral desmopressin (DDAVP) in hydrated normal subjects
Author(s) -
Rittig S,
Jensen A. R,
Jensen K. T,
Pedersen E. B
Publication year - 1998
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1046/j.1365-2265.1998.3401166.x
Subject(s) - desmopressin , antidiuretic , urine osmolality , cmax , medicine , endocrinology , pharmacokinetics , crossover study , ingestion , urine , meal , oral administration , vasopressin , placebo , alternative medicine , pathology
OBJECTIVE The effect of food ingestion on the gastrointestinal absorption and antidiuretic action of oral desmopressin. An oral preparation of desmopressin, a synthetic analogue of vasopressin, has recently become available for clinical use. DESIGN A randomized, single‐blind, crossover study with four treatment arms. Day A, no meal + placebo; B, no meal + 400 μg oral desmopressin; C, standard meal + 400 μg oral desmopressin; D, standard meal + 400 μg oral desmopressin after 1.5 hours. Plasma desmopressin was measured every 15–30 minutes for 6 hours after drug intake. An intravenous hydration regimen was employed on each study day. SUBJECTS Sixteen healthy, non‐smoking, men aged 20–35 years (mean 27.8 years). MEASUREMENTS Plasma desmopressin concentrations were measured throughout each study day to calculate the area under the desmopressin plasma‐concentration–time curve to infinity (AUC inf ), the maximum plasma desmopressin concentration (C max ), the time at which C max was reached (T max ) and the time at which plasma desmopressin was first detected (T lag ). Urine volume, urine osmolality and plasma sodium concentrations were also measured at specified times on each study day. RESULTS The total absorption of oral desmopressin, reflected by the AUC inf , was significantly higher when taken during the fasting state (day B) compared with its administration with or 1.5 hours after a standard meal (days C and D). In addition, C max was higher and both T max and T lag were shorter on day B compared with days C and D. No effect of food ingestion was observed on the pharmacodynamics of oral desmopressin: urine volume was decreased and urine osmolality was increased to similar extents on all active treatment days (B, C and D). No significant reductions in plasma sodium concentrations (a safety parameter) was observed during the trial. CONCLUSIONS The gastrointestinal absorption of desmopressin is reduced and delayed if administered with or 1.5 hours after a meal. This decreased absorption of desmopressin did not have an impact on the antidiuretic action of the drug since all treatment regimens elicted a maximal response. It is possible that administration of desmopressin in the fasting state may prolong its duration of action.