Desmopressin dosing in children using real-world data and pharmacokinetic/pharmacodynamic model simulations

Background: Variability in pediatric dosing of desmopressin (ddAVP) in AVP-deficiency (AVP-D) is well-documented but dosing recommendations are limited. This study evaluates and optimizes ddAVP dosing regimens in children with AVP-D using pharmacokinetic and pharmacodynamic (PK/PD) simulations. Methods: Retrospective electronic health record review was done to identify children (<18 years) with AVP-D on ddAVP evaluated in the outpatient setting using ICD 9 and 10 codes. A previously developed PK/PD model from Michelet et al was used to simulate ddAVP concentrations and urine rates based on a child's age and ddAVP dose. The effects of demographic characteristics (age, weight, etc.) on dose and urine rate were investigated through simulations to optimize doses of ddAVP for children who were wet overnight. Result: A total of 276 dosing records were identified among 53 children with AVP-D. Simulations indicated that in children under 5 years of age who were wet overnight, increasing the outpatient dose to 50 mcg was predicted to decrease urine rate to a pattern similar to those who remained dry. Conclusion: An initial outpatient dose of at least 50 mcg for children between 1 and 5 years of age would improve efficacy of ddAVP.