Bioavailability of dexamethasone. II. Dexamethasone phosphate

Area of Science:

• Pharmacokinetics
• Drug Metabolism

Background:

• Dexamethasone phosphate (DP) is an intravenous prodrug.
• Understanding DP to dexamethasone free alcohol (DA) conversion is crucial for dosing.

Purpose of the Study:

• To quantify the in vivo conversion of DP to DA in humans.
• To determine the kinetics of DP hydrolysis.
• To compare parenteral DP formulations.

Main Methods:

• Radioimmunoassay (RIA) was used to measure plasma DP and DA levels.
• Intravenous DP administration in human subjects.
• Pharmacokinetic modeling to determine conversion rates and disposition parameters.

Main Results:

• Plasma DA levels showed a linear dose-response relationship with DP dosage (0.05-2.0 mg/kg).
• Overall DP to DA conversion was approximately 90%.
• The rate constant for DP conversion (4.03 hr-1) was significantly faster than in vitro hydrolysis.

Conclusions:

• DP is rapidly hydrolyzed to DA in vivo, primarily within highly perfused organs.
• The central kinetic compartment likely represents organs responsible for DP hydrolysis.
• Current and experimental DP formulations showed comparable pharmacokinetic parameters.