Pulmonary Delivery of Vancomycin Dry Powder Aerosol to Intubated Rabbits.
Antibiotic multiresistant pneumonia is a risk associated with long-term mechanical ventilation. Vancomycin is commonly prescribed for methicillin-resistant Staphylococcus aureus infections; however, current formulations of vancomycin are only given intravenously. High doses of vancomycin have been associated with severe renal toxicity. In this study, we characterized dry powder vancomyin as a potential inhaled therapeutic aerosol and compared pharmacokinetic profiles of iv and pulmonary administered vancomycin in intubated rabbits through an endotracheal tube system. Cascade impaction studies indicated that using an endotracheal tube, which bypasses deposition in the mouth and throat, increased the amount of drug entering the lung. Bypassing the endotracheal tube with a catheter further enhanced drug deposition in the lung. Interestingly, intubated rabbits administered 1 mg/kg vancomycin via inhalation had similar AUC to rabbits that were administered 1 mg/kg vancomycin via a single bolus iv infusion; however, inhalation of vancomycin reduced Cmax and increased Tmax, indicating that inhaled vancomycin resulted in more sustained pulmonary levels of vancomycin. Collectively, these results suggested that dry powder vancomycin can successfully be delivered by pulmonary inhalation in intubated patients. Furthermore, as inhaled vancomycin is delivered locally to the site of pulmonary infection, this delivery route could reduce the total dose required for therapeutic efficacy and simultaneously reduce the risk of renal toxicity by eliminating the high levels of systemic drug exposure required to push the pulmonary dose to therapeutic thresholds during iv administration.
†Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, United States.
Bradley P
BP
Sullivan
†Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, United States.|§Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
Nashwa
N
El-Gendy
†Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, United States.
Christopher
C
Kuehl
†Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, United States.|∥Department of Chemical and Petroleum Engineering, University of Kansas, Lawrence, Kansas 66045, United States.
Cory
C
Berkland
D000280:Administration, Inhalation; D061605:Administration, Intravenous; D000336:Aerosols; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D058995:Dry Powder Inhalers; D005260:Female; D007442:Intubation, Intratracheal / Q000009:adverse effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D011208:Powders; D011817:Rabbits; D014640:Vancomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D000336:Aerosols; D000900:Anti-Bacterial Agents; D011208:Powders; D014640:Vancomycin
endotracheal tube; modified insufflator; pharmacokinetics; pulmonary delivery; vancomycin; ventilated patients