Diazoxide clinical pharmacology

Diazoxide
PROGLYCEM® FDA Package Insert
Indications and Usage
Dosage and Administration
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Overdosage
Description
Clinical Pharmacology
Nonclinical Toxicology
How Supplied/Storage and Handling
Labels and Packages
Clinical Trials on Diazoxide
ClinicalTrials.gov

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]

Clinical Pharmacology

Diazoxide administered orally produces a prompt dose-related increase in blood glucose level, due primarily to an inhibition of insulin release from the pancreas, and also to an extrapancreatic effect.

The hyperglycemic effect begins within an hour and generally lasts no more than eight hours in the presence of normal renal function.

PROGLYCEM® decreases the excretion of sodium and water, resulting in fluid retention which may be clinically significant.

The hypotensive effect of diazoxide on blood pressure is usually not marked with the oral preparation. This contrasts with the intravenous preparation of diazoxide (seeADVERSE REACTIONS).

Other pharmacologic actions of PROGLYCEM® include increased pulse rate; increased serum uric acid levels due to decreased excretion; increased serum levels of free fatty acids' decreased chloride excretion; decreased para-aminohippuric acid; (PAH) clearance with no appreciable effect on glomerular filtration rate.

The concomitant administration of a benzothiazide diuretic may intensify the hyperglycemic and hyperuricemic effects of PROGLYCEM®. In the presence of hypokalemia, hyperglycemic effects are also potentiated.

PROGLYCEM®-induced hyperglycemia is reversed by the administration of insulin or tolbutamide. The inhibition of insulin release by PROGLYCEM® is antagonized by alpha-adrenergic blocking agents.

PROGLYCEM® is extensively bound (more than 90%) to serum proteins, and is excreted in the kidneys. The plasma half-life following I.V. administration is 28 ± 8.3 hours. Limited data on oral administration revealed a half-life of 24 and 36 hours in two adults. In four children aged four months to six years, the plasma half-life varied from 9.5 to 24 hours on long-term oral administration. The half-life may be prolonged following overdosage, and in patients with impaired renal function.