Posaconazole plasma concentrations in critically ill patients

Area of Science:

• Pharmacology
• Critical Care Medicine
• Infectious Diseases

Background:

• Posaconazole is a broad-spectrum azole antifungal with a known safety profile.
• Previous pharmacokinetic studies were conducted in healthy volunteers, not critically ill patients.

Purpose of the Study:

• To evaluate the pharmacokinetics of oral posaconazole in critically ill patients.
• To compare posaconazole plasma concentrations with established therapeutic targets.

Main Methods:

• 27 intensive care unit patients received either 400 mg twice daily or 200 mg 4 times daily posaconazole.
• Plasma samples were collected for pharmacokinetic analysis post-initial dose and at steady-state.
• Posaconazole concentrations were compared against prophylaxis and treatment effect targets.

Main Results:

• Both dosing regimens resulted in low mean steady-state plasma concentrations (Cmin) and total exposure (AUC0-t).
• Only 17% of patients reached the target Cmin for prophylaxis; one patient met the treatment target.
• Systemic exposure appeared subtherapeutic in most patients, potentially due to poor absorption or drug interactions.

Conclusions:

• Oral posaconazole exposure is likely subtherapeutic in critically ill patients.
• An intravenous formulation may be necessary for effective use in this population.
• Therapeutic drug monitoring is crucial to prevent treatment failure due to low posaconazole levels.