Population Pharmacokinetics of Diazoxide in Children with Hyperinsulinemic Hypoglycemia

Rika Kizu, Kazuko Nishimura, Reiko Sato, Kenjiro Kosaki, Toshiaki Tanaka, Yusuke Tanigawara, Tomonobu Hasegawa

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 × 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.

Original languageEnglish
Pages (from-to)316-323
Number of pages8
JournalHormone Research in Paediatrics
Volume88
Issue number5
DOIs
Publication statusPublished - 2017 Nov 1

Keywords

  • Diazoxide
  • Hyperinsulinemic hypoglycemia
  • Population pharmacokinetics

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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