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Pediatric Pharmacology of Desmopressin in Children with Enuresis: A Comprehensive Review

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Abstract

Desmopressin is a synthetic analogue of the natural antidiuretic hormone arginine vasopressin. Over the years, it has been clinically used to manage nocturnal polyuria in children with enuresis. Various pharmaceutical formulations of desmopressin have been commercialized for this indication—nasal spray, nasal drops, oral tablet and oral lyophilizate. Despite the fact that desmopressin is a frequently prescribed drug in children, its use and posology is based on limited pediatric data. This review provides an overview of the current pediatric pharmacological data related to the different desmopressin formulations, including their pharmacokinetics, pharmacodynamics and adverse events. Regarding the pharmacokinetics, a profound food effect on the oral bioavailability was demonstrated as well as different plasma concentration–time profiles (double absorption peak) of the desmopressin lyophilizate between adults and children. Literature about maturational differences in distribution, metabolism and excretion of desmopressin is rather limited. Regarding the pharmacodynamics, formulation/dose/food effect and predictors of response were evaluated. The lyophilizate is the preferred formulation, but the claimed bioequivalence in adults (200 µg tablet and 120 µg lyophilizate), could not be readily extrapolated to children. Prescribing the standard flat-dose regimen to the entire pediatric population might be insufficient to attain response to desmopressin treatment, whereby dosing schemes based on age and weight were proposed. Moreover, response to desmopressin is variable, whereby complete-, partial- and non-responders are reported. Different reasons were enumerated that might explain the difference in response rate to desmopressin observed: different pathophysiological mechanisms, bladder capacity and other predictive factors (i.e. breast feeding, familial history, compliance, sex, etc.). Also, the relapse rate of desmopressin treatment was high, rendering it necessary to use a pragmatic approach for the treatment of enuresis, whereby careful consideration of the position of desmopressin within this treatment is required. Regarding the safety of the different desmopressin formulations, the use of desmopressin was generally considered safe, but additional measures should be taken to prevent severe hyponatremia. To conclude the review, to date, major knowledge gaps in pediatric pharmacological aspects of the different desmopressin formulations still remain. Additional information should be collected about the clinical relevance of the double absorption peak, the food effect, the bioequivalence/therapeutic equivalence, the pediatric adapted dosing regimens, the study endpoints and the difference between performing studies at daytime or at nighttime. To fill in these gaps, additional well designed pharmacokinetic and pharmacodynamic studies in children should be performed.

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Acknowledgements

The help of Charlotte Van Herzeele and Pauline De Bruyne in retrieving possible literature for this review was gratefully appreciated.

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All authors contributed to the review conception and design. The first draft of the manuscript was written by Elke Gasthuys and Lien Dossche and all authors commented on previous versions of the manuscript. All authors critically revised and approved the final manuscript.

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Correspondence to Elke Gasthuys.

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Elke Gasthuys, Lien Dossche and Robin Michelet were supported by a doctoral fellowship from the Agency for Innovation by Science and Technology in Flanders (IWT) through the ‘SAFEPEDRUG’ project (IWT/SBO 130033). Jens Peter Nørgaard is supported by a Ferring Grant (Guest professor).

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Elke Gasthuys, Lien Dossche, Robin Michelet, Jens Peter Nørgaard, Mathias Devreese, Siska Croubels, An Vermeulen, Jan Van Bocxlaer and Johan Vande Walle declare that they have no conflict of interest related to the manuscript.

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Gasthuys, E., Dossche, L., Michelet, R. et al. Pediatric Pharmacology of Desmopressin in Children with Enuresis: A Comprehensive Review. Pediatr Drugs 22, 369–383 (2020). https://doi.org/10.1007/s40272-020-00401-7

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