ESPN 51th Annual Meeting

ESPN 2018


 
POPULATION PHARMACOKINETIC MODELING OF A DESMOPRESSIN ORAL LYOPHILISATE IN GROWING PIGLETS AS A MODEL FOR THE PEDIATRIC POPULATION
Elke Gasthuys 2 Ann Vermeulen 4 Siska Croubels 2 Pauline Debruyne 1 Joske Millecam 2 Johan Vande Walle 1 Mathias Devreeze 2

1- Safepedrug, Ugent,GEO2
2- Safepedug,Veterinary School, Ugent
3- Veterinary Medicine
4- Faculty of Pharmaceutical Sciences, UGent
 
Introduction:

Pediatric clinical trial design is mainly extrapolated from adult data, not taking in account pediatric specific characterstics, because absence of appropriate pediatric animal models as well as ethically not acceptable to perform studies in healthy children. This research line aims to fill the gap be juvenile animal drug.  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. 

Material and methods:

 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. 

Results:

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. 

Conclusions:

Desmopressin demonstrated two-compartmental PK, with a dual, sequential absorption process, and linear elimination. 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. The size dependency in the animal model would have changed the dose-finding studies in children in an more appropriate way (no size dependency).