Objective To study the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of desmopressin (dDAVP) oral lyophilisate in children below the age of 8 years with special emphasis on age-related and size-related differences in bioavailability.
Design Open label, non-randomised, interventional PK and PD trial.
Setting Single-centre study.
Patients Children (age: 6 months to 8 years) with nocturnal polyuria, including both children with uropathy or nephropathy (glomerular filtration rate >60 mL/min/1.73 m²) and children (age: 5–8 years) with severe monosymptomatic nocturnal enuresis, who were unresponsive to treatment with 400 µg of the dDAVP tablet for at least 1 month.
Interventions After a water load, dDAVP was administered sublingually as a single dose of oral lyophilisate. Subsequently, blood and urine samples were collected until 7 hours post-administration.
Main outcome measures Non-compartmental analysis of PK parameters was performed based on dDAVP concentrations in both plasma and urine. To evaluate the effect of dDAVP lyophilisate (PD parameters), the urinary concentration capacity (urine osmolality (mOsm/kg)) and antidiuretic effect (diuresis rate (mL/kg/h)) were calculated.
Results The PK data support the need for size-dependent dosing in children. Body weight was shown to be a significant covariate for apparent clearance (CL/F) and apparent volume of distribution (Vd/F). A double absorption peak of dDAVP lyophilisate in the first 2 hours post-administration was demonstrated.
Conclusions For the first time, a double absorption profile of dDAVP lyophilisate was found in children, questioning extrapolation of bioequivalence from adults towards children. Moreover, the need for size-adapted dosing regimens of dDAVP lyophilisate in young children is indicated.
Trial registration number NTC02584231.
- desmopressin acetate oral disintegrating tablets
- monosymptomatic nocturnal enuresis
- renal concentration test
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Contributors LD, RM, CVH, EG, PDB, AV and JvdW conceptualised the study. LD and JvdW performed the clinical trial and collected the data. LD and JvdW analysed the data, and SR, RM, AV and EG provided help with the interpretation of the data for the work. LD performed the literature search, drafted the initial manuscript and revised subsequent drafts. RM, PDB, CVH, EG, SR, AV and JvdW critically reviewed and revised the manuscript.
Funding This study was supported by the ‘Agency for Innovation by Science and Technology in Flanders (IWT)’ through the ‘SAFE-PEDRUG’ project (IWT-SBO 130033).
Competing interests LD, CVH, EG and PDB received a travel reimbursement from Ferring Pharmaceuticals for a presentation at the Ghent-Aarhus Springschool. SR and JvdW received consulting fees and travel reimbursements from Ferring Pharmaceuticals. AV is an employee of Johnson & Johnson and holds stock/stock options from J&J. RM has no potential conflicts of interest that might be relevant to this manuscript.
Patient consent for publication Not required. Written informed consent was obtained from all parents and/or legal guardians before study participation.
Ethics approval The study was approved by the local Ethics Committee (EC/2015/0616), EudraCT (2014-005200-13). The study was conducted in accordance with the International Conference on Harmonization Guideline for Good Clinical Practice.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement The data that support the findings of this study are available from the corresponding author, on reasonable request.
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