Kizu R, et al. – The scientists explored the pharmacokinetics of diazoxide in children with hyperinsulinemic hypoglycemia (HI). They established a population pharmacokinetic model for diazoxide in children with HI. They illustrated that the potential risk of diabetes mellitus and/or hyperglycemia increases when serum concentrations of diazoxide exceed 100 μg/mL.

Methods

• The scientists gathered 81 blood samples from 22 children with HI.
• For population pharmacokinetic analysis, measured serum diazoxide concentrations were used.
• With the aid of nonlinear mixed–effects model analysis, patient factors influencing pharmacokinetics were determined.
• Relationships between drug exposure and adverse drug reactions were also examined.

Results

• By a 1–compartment model, diazoxide disposition in the body was described.
• 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.
• Between severity of hirsutism and diazoxide concentration, no significant correlation was reported.