Abstract
Desmopressin is used to treat primary nocturnal enuresis in children. Over the years, various formulations of desmopressin were commercialized of which the sublingual melt tablet is preferred in the pediatric population, despite the lack of full PK studies in this population. A full PK study was performed in growing conventional piglets to evaluate if this juvenile animal model can provide supplementary information to complement the information gap in the pediatric population. A desmopressin sublingual melt tablet (120 μg) was administered to 32 male piglets aged 8 days, 4 weeks, 7 weeks, and 6 months (each group n = 8). Population PK (pop-PK) analysis was performed to derive the PK parameters, the between- and within-subject variabilities and the effects of covariates. Desmopressin demonstrated two-compartmental PK, with a dual, sequential absorption process, and linear elimination. Body weight was the only significant covariate on clearance and on apparent volume of distribution of the central compartment. In human pediatric trials, no double peak in the absorption phase was observed in the plasma concentration-time curves, possibly due to the sparse sampling strategy applied in those pediatric studies. Therefore, it is recommended to perform additional studies, based on the sampling protocol applied in the current study.
Highlights
Pediatric non-clinical and clinical studies are pivotal to investigate inter alia age-dependent dosing schedules and ageappropriate formulations
All piglets received a desmopressin oral lyophilisate under identical circumstances and no general side effects were observed during the experiment
The best description of the plasma concentrationtime profiles of desmopressin in growing piglets was obtained with a two-compartmental disposition model combined with a dual input function for the absorption
Summary
Pediatric non-clinical and clinical studies are pivotal to investigate inter alia age-dependent dosing schedules and ageappropriate formulations. De Bruyne et al (2014) applied a sparse sampling protocol after administration of conventional tablets (200 μg) and oral lyophilisates (120 μg) containing desmopressin to 23 children (5–18 years) suffering from monosymptomatic nocturnal enuresis. The full PK profiles were obtained through pop-PK simulation (Michelet et al, 2016), but likely do not capture all characteristics of desmopressin’s PK, since the original studies applied a sparse sampling protocol It is in this respect, that trials using pediatric animal models, such as the conventional piglet, might provide supplementary information to complement the information gap since full PK studies can be performed
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