Journal
HORMONE RESEARCH IN PAEDIATRICS
Volume 88, Issue 5, Pages 316-323Publisher
KARGER
DOI: 10.1159/000478696
Keywords
Diazoxide; Population pharmacokinetics; Hyperinsulinemic hypoglycemia
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Background: Diazoxide is the first-line treatment for pediatric hyperinsulinemic hypoglycemia (HI). This study aimed to elucidate the pharmacokinetics of diazoxide in children with HI. Methods: We obtained 81 blood samples from 22 children with HI. Measured serum diazoxide concentrations were used for population pharmacokinetic analysis. Patient factors influencing pharmacokinetics were estimated using nonlinear mixed-effects model analysis. Relationships between drug exposure and adverse drug reactions were also investigated. Results: Diazoxide disposition in the body was described by a 1-compartment model. Oral clearance (CL/F) and the volume of distribution were proportional to body weight (WT), as expressed by CL/F in males (liters/h) = 0.0358 + 0.00374 x WT (kg). CL/F in females was 39% greater than that in males. Steady-state concentrations of diazoxide were similar following twice-and 3 times-daily dosing when the total daily doses were comparable. A patient whose serum diazoxide concentration exceeded 100 mu g/mL over a 4-month period developed hyperglycemia. No significant correlation was observed between severity of hirsutism and diazoxide concentration. Conclusion: We have proposed for the first time a population pharmacokinetic model for diazoxide in children with HI. The potential risk of diabetes mellitus and/or hyperglycemia increases when serum concentrations of diazoxide exceed 100 mu g/mL. (C) 2017 The Author(s) Published by S. Karger AG, Basel
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