Oral Drug Absorption and Drug Disposition in Critically Ill Cardiac Patients

Area of Science:

• Pharmacology
• Critical Care Medicine
• Cardiology

Background:

• Critically ill cardiac patients may receive medications via parenteral or enteral routes.
• Altered drug absorption and metabolism in this population are not well understood.
• This study investigates drug pharmacokinetics in cardiogenic shock patients.

Purpose of the Study:

• To analyze drug absorption and metabolism in critically ill cardiac patients.
• To evaluate the pharmacokinetics of esomeprazole in patients with cardiogenic shock.
• To compare drug pharmacokinetics in critically ill patients versus controls.

Main Methods:

• Analyzed esomeprazole pharmacokinetics in critically ill patients with cardiogenic shock and controls.
• Administered esomeprazole orally, via nasogastric tube, and intravenously.
• Assessed drug absorption, metabolism (CYP3A4 and CYP2C19 activity), and metabolite ratios.

Main Results:

• Esomeprazole plasma concentrations and AUC were approximately 50% lower in critically ill patients.
• Drug absorption remained compromised up to seven days post-shock and on day one post-surgery.
• CYP3A4 activity was reduced in critically ill patients, correlating negatively with CRP levels.

Conclusions:

• Gastrointestinal drug absorption is significantly reduced in critically ill cardiac patients.
• Intravenous administration of vital medications is recommended to ensure adequate bioavailability.
• Hepatic metabolism via CYP3A4 may be impaired following cardiogenic shock.