Population Pharmacokinetics of Diazoxide in Children with Hyperinsulinemic Hypoglycemia.

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.

journal_name

Horm Res Paediatr

authors

Kizu R,Nishimura K,Sato R,Kosaki K,Tanaka T,Tanigawara Y,Hasegawa T

doi

10.1159/000478696

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

316-323

issue

5

eissn

1663-2818

issn

1663-2826

pii

000478696

journal_volume

88

pub_type

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