title: Pharmacokinetics of desmopressin administered as tablet and oral lyophilisate formulation in children with monosymptomatic nocturnal enuresis.
abstract: Desmopressin 120 μg oral lyophilisate and 200 μg tablet are considered bioequivalent, based on extrapolation of studies in a limited number of adults and on one dose-finding study of desmopressin oral lyophilisate in children. However, no comparative pharmacokinetic study in children was executed confirming this statement. No data are available on the influence of food intake on the bioavailability of desmopressin tablet in a pediatric setting, although studies in adults have documented that food intake results in a significantly lower desmopressin plasma concentration. In this study, we analyzed plasma concentrations of desmopressin oral lyophilisate and tablet with concomitant food intake. Twenty-three children with monosymptomatic nocturnal enuresis (mean age, 12.7 years) were recruited. Two tests were performed on two separate days in identical conditions with a standardized food and fluid intake. Desmopressin was administered as desmopressin tablet or desmopressin oral lyophilisate immediately after a meal. Desmopressin plasma concentration was measured at 1 h, 2 h, and 6 h postdosing. No significant difference in plasma concentration of 120 μg desmopressin oral lyophilisate and 200 μg tablet was demonstrated, even with concomitant food intake. A significant difference in variability was found, identifying a smaller variance for desmopressin oral lyophilisate plasma concentrations at all time points. This study demonstrates comparable plasma levels for desmopressin oral lyophilisate, despite the lower dose. The dosage for desmopressin oral lyophilisate is more predictable due to the significantly smaller variance. Therefore, desmopressin oral lyophilisate seems more suitable, especially in the younger age group for which time interval between dinner and drug administration is limited.
authors.affiliation: Department of Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 3K12D, De Pintelaan 185, 9000, Ghent, Belgium, pauline.debruyne@ugent.be.
authors.forename: Pauline
authors.initials: P
authors.lastname: De Bruyne
authors.forename: Ann
authors.initials: A
authors.lastname: De Guchtenaere
authors.forename: Charlotte
authors.initials: C
authors.lastname: Van Herzeele
authors.forename: Ann
authors.initials: A
authors.lastname: Raes
authors.forename: Jo
authors.initials: J
authors.lastname: Dehoorne
authors.forename: Piet
authors.initials: P
authors.lastname: Hoebeke
authors.forename: Erik
authors.initials: E
authors.lastname: Van Laecke
authors.forename: Johan
authors.initials: J
authors.lastname: Vande Walle
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D001682:Biological Availability; D002648:Child; D018592:Cross-Over Studies; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D018565:Food-Drug Interactions; D005612:Freeze Drying; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D053206:Nocturnal Enuresis / Q000097:blood* / Q000188:drug therapy*; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D013607:Tablets; D003894:Deamino Arginine Vasopressin