Desmopressin oral lyophilisate in young children: new insights in pharmacokinetics and pharmacodynamics

Author:

Dossche LienORCID,Michelet RobinORCID,De Bruyne Pauline,Van Herzeele Charlotte,Gasthuys Elke,Rittig Søren,Vermeulen An,Vande Walle Johan

Abstract

ObjectiveTo 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.DesignOpen label, non-randomised, interventional PK and PD trial.SettingSingle-centre study.PatientsChildren (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.InterventionsAfter 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 measuresNon-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.ResultsThe 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.ConclusionsFor 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 numberNTC02584231.

Funder

Agentschap voor Innovatie door Wetenschap en Technologie

Publisher

BMJ

Subject

Pediatrics, Perinatology and Child Health

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1. Potential clinical applications of current and future oral forms of desmopressin (Review);Experimental and Therapeutic Medicine;2024-05-29

2. DESMOPRESSIN;Prescriber's Guide – Children and Adolescents;2024-05-02

3. Computer simulations in pharmacokinetics;Physico-Chemical Aspects of Dosage Forms and Biopharmaceutics;2024

4. Application of preclinical juvenile animal models;Essentials of Translational Pediatric Drug Development;2024

5. Case 14: The boy whose bed was always wet: nocturnal enuresis in a child;Case Studies: Stahl's Essential Psychopharmacology;2023-11-09

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