Pulmonary Delivery of Vancomycin Dry Powder Aerosol to Intubated Rabbits

Area of Science:

• Pulmonary Drug Delivery
• Pharmacokinetics
• Infectious Diseases

Background:

• Antibiotic-resistant pneumonia is a significant risk for patients on long-term mechanical ventilation.
• Current intravenous vancomycin formulations for methicillin-resistant Staphylococcus aureus (MRSA) infections can cause severe renal toxicity due to high systemic doses.
• There is a need for safer and more effective vancomycin delivery methods for pulmonary infections.

Purpose of the Study:

• To characterize dry powder vancomycin as an inhaled therapeutic aerosol.
• To compare the pharmacokinetic profiles of intravenous (IV) versus pulmonary-administered vancomycin in intubated rabbits.
• To evaluate the potential of inhaled vancomycin to reduce dose and systemic toxicity.

Main Methods:

• Dry powder vancomycin was formulated as an aerosol for pulmonary delivery.
• Pharmacokinetic studies were conducted in intubated rabbits comparing IV and inhaled vancomycin administration via an endotracheal tube system.
• Cascade impaction was used to assess drug deposition in the lungs, with and without a catheter bypassing the endotracheal tube.

Main Results:

• Using an endotracheal tube increased lung drug deposition by bypassing the upper airway.
• Further bypassing the endotracheal tube with a catheter enhanced lung drug deposition.
• Inhaled vancomycin (1 mg/kg) resulted in similar area under the curve (AUC) as IV vancomycin (1 mg/kg) but with a reduced peak concentration (Cmax) and increased time to peak concentration (Tmax), indicating sustained pulmonary levels.

Conclusions:

• Dry powder vancomycin can be effectively delivered via pulmonary inhalation in intubated patients.
• Inhaled vancomycin provides sustained local drug levels in the lungs.
• This delivery route may reduce the required total dose and mitigate renal toxicity associated with high systemic IV vancomycin exposure.