Evidence map›Paper›PMID 29198064›Full record

ArticleEuropean journal of clinical pharmacology2018

Claiming desmopressin therapeutic equivalence in children requires pediatric data: a population PKPD analysis.

Robin Michelet, Lien Dossche, Charlotte Van Herzeele, Jan Van Bocxlaer, An Vermeulen, Johan Vande Walle, SAFE-PEDRUG consortium

Abstract readComparative StudyControlled Clinical TrialEquivalence Trial
PubMed Publisher
In one paragraph

Article in European journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Generic drug products in paediatrics: Where are the data?British journal of clinical pharmacology · 2019
    Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Robin MicheletLaboratory of Medical Biochemistry and Clinical Analysis, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium. robin.michelet@ugent.be.
Lien DosscheDepartment of Pediatric Nephrology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. lien.dossche@ugent.be.ORCID http://orcid.org/0000-0003-1030-9848
Charlotte Van HerzeeleDepartment of Pediatric Nephrology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.
Jan Van BocxlaerLaboratory of Medical Biochemistry and Clinical Analysis, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
An VermeulenLaboratory of Medical Biochemistry and Clinical Analysis, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
Johan Vande WalleDepartment of Pediatric Nephrology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.
SAFE-PEDRUG consortium
Ghent University · BEGhent University Hospital · BE

Funding

Agentschap voor Innovatie door Wetenschap en Technologie 'SAFE-PEDRUG' project (IWT-SBO 130033)
6 · The paper itself

Abstract

purposeFor a new formulation of a drug, only pharmacokinetic bioequivalence with the original formulation has to be demonstrated in healthy, young adults. However, "children are not small adults," and to guarantee a safe and effective treatment, age-adapted drug development is required. Desmopressin, a vasopressin analogue prescribed for nocturnal enuresis in children, was studied as an example formulation first developed in adults and then extrapolated to a pediatric indication.

methodsPopulation pharmacokinetic and pharmacodynamic modeling was used to analyze previously published desmopressin data of 18 children suffering from nocturnal enuresis. The main objective was the comparison of the therapeutic equivalence of two desmopressin formulations: tablet and lyophilisate. The measurements for pharmacokinetics and pharmacodynamics were respectively plasma desmopressin concentration and urine osmolality and diuresis.

resultsThe half maximal inhibitory concentration for inhibition of urine production was 0.7 pg/mL lower for the lyophilisate than for the tablet. The effect of formulation on the half maximal inhibitory concentration seems to suggest that the 120-μg lyophilisate has a more pronounced effect on the urine volume and osmolality than the 200-μg tablet, even when the same exposure is achieved.

conclusionsA new indirect response model for desmopressin was constructed and validated, using a previously built pharmacokinetic model and additional pharmacodynamic data. In order to draw solid conclusions regarding the efficacy and safety of desmopressin in children, pharmacokinetics and pharmacodynamics data should be analyzed together. This study adds proof to potential differences in pediatric and adult pharmacokinetic and pharmacodynamic properties of desmopressin and exemplifies the need for pediatric clinical trials, not only for every new drug but also for every new formulation.

Indexed as

Drug CompoundingModels, BiologicalAdministration, SublingualAdolescentAge FactorsAntidiuretic AgentsChildCross-Over StudiesDeamino Arginine VasopressinFemaleFreeze DryingHumansKidney Concentrating AbilityMaleNeeds AssessmentNocturnal EnuresisAntidiuretic AgentsDeamino Arginine VasopressinTablets1-Deamino-8-D-arginine vasopressin (dDAVP)BioequivalenceChildrenLyophilisatePKPD modelingTablet

Identifiers

PMID29198064
OpenAlexW2775383616

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.