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- Title
Population Pharmacokinetics of Diazoxide in Children with Hyperinsulinemic Hypoglycemia.
- Authors
Kizu, Rika; Nishimura, Kazuko; Sato, Reiko; Kosaki, Kenjiro; Tanaka, Toshiaki; Tanigawara, Yusuke; Hasegawa, Tomonobu
- Abstract
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 μg/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 μg/mL.
- Subjects
HYPOGLYCEMIA in children; DIAZOXIDE; PHARMACOKINETICS
- Publication
Hormone Research in Paediatrics, 2017, Vol 88, Issue 5, p316
- ISSN
1663-2818
- Publication type
Article
- DOI
10.1159/000478696