Drug interaction: diazoxide and diphenylhydantoin

Area of Science:

• Pharmacology
• Pediatrics
• Clinical Pharmacy

Background:

• Hypoglycemia and convulsions are serious conditions in children.
• Diphenylhydantoin (phenytoin) is used to manage seizures.
• Diazoxide is used to treat hypoglycemia.

Purpose of the Study:

• To investigate the interaction between diazoxide and diphenylhydantoin in pediatric patients.
• To determine the effect of diazoxide on serum diphenylhydantoin levels.

Main Methods:

• Two pediatric patients with hypoglycemia and convulsions were treated concurrently with diazoxide and diphenylhydantoin.
• Serum diphenylhydantoin levels were monitored before, during, and after diazoxide administration.
• Plasma protein binding of diphenylhydantoin was assessed.

Main Results:

• Therapeutic serum diphenylhydantoin levels were not achieved at high doses when co-administered with diazoxide.
• Discontinuation of diazoxide allowed therapeutic diphenylhydantoin levels to be reached at lower doses.
• Reintroduction of diazoxide led to undetectable diphenylhydantoin levels.

Conclusions:

• Diazoxide significantly reduces serum concentrations of diphenylhydantoin in pediatric patients.
• This interaction may be due to increased diphenylhydantoin metabolism or decreased plasma protein binding induced by diazoxide.
• Careful monitoring of diphenylhydantoin levels is essential when used concurrently with diazoxide in children.