Population Pharmacokinetics of Diazoxide in Children with Hyperinsulinemic Hypoglycemia
| Autor: | Kenjiro Kosaki, Toshiaki Tanaka, Tomonobu Hasegawa, Kazuko Nishimura, Yusuke Tanigawara, Reiko Sato, Rika Kizu |
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| Rok vydání: | 2017 |
| Předmět: |
Male
medicine.medical_specialty Adolescent Endocrinology Diabetes and Metabolism Population medicine.disease_cause Models Biological 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Endocrinology Pharmacokinetics 030225 pediatrics Diabetes mellitus Internal medicine Diazoxide Humans Medicine Dosing Child Hyperinsulinemic hypoglycemia education hirsutism Volume of distribution Original Paper education.field_of_study Dose-Response Relationship Drug business.industry Infant Newborn Infant medicine.disease Child Preschool Pediatrics Perinatology and Child Health Congenital Hyperinsulinism Female business medicine.drug |
| Zdroj: | Hormone Research in Paediatrics. 88:316-323 |
| ISSN: | 1663-2826 1663-2818 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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