Lung and serum teicoplanin concentration after aerosol and intravenous administration in a rat model
Emmanuelle Mercier1, François Darrouzain, Jerome Montharu
11 Université François Rabelais , EA 6305, F-37032 Tours, France .
Background:
Ventilator-associated pneumonia (VAP) caused by methicillin-resistant Staphylococcus aureus is a major cause of mortality in mechanically ventilated patients. Nebulization of teicoplanin is an alternative way of administration that may provide higher lung tissue concentrations than intravenous (IV) delivery. The aim of this study was to compare the administration of teicoplanin via aerosol with the IV route by measuring the lung and the serum teicoplanin concentrations in a rat model.
Methods:
Eighty healthy male Sprague-Dawley rats were anesthetized and received a single dose of teicoplanin by the IV or aerosol route. After sacrifice, lung and blood samples were collected and teicoplanin concentrations were measured with fluorescence polarization. A noncompartmental approach was used. The area under the concentration curve/minimal inhibition concentration ratio (AUC/MIC), AUC, absorbed fraction, mean residence time (MRT), and mean absorption time (MAT) of teicoplanin were calculated.
Results:
Mean±SD lung tissue concentrations of teicoplanin in the aerosol group were significantly higher than those in the IV group (p<0.0001). The mean lung tissue concentration achieved at 15 min was 1.94±1.33 mg/g in the aerosol group and 0.04±0.01 mg/g in the IV group. The mean AUClung was 67.4 mg hr(-1)g(-1) after aerosol and 0.8 mg hr(-1)g(-1) after the IV route. In the aerosol group, AUCserum/MIC ratio was 605/2, and in the IV route, AUCserum/MIC ratio was 682/2. MAT was longer after aerosol than after the IV route (0.91 hr versus 0.06 hr), and MRT was longer after aerosol than after IV bolus administration (6.52 hr versus 5.61 hr).
Conclusion:
Teicoplanin concentrations in the lung tissue of the rat model were significantly higher by the aerosol route than by the IV route. The AUClung after nebulization was 84 times higher than delivery by the IV route, and the AUClung/MIC ratio after nebulization met the recommended target to eradicate Staphylococcus aureus. Administration of teicoplanin by the aerosol route could represent one of the new therapeutic weapons of the treatment of the VAP.
Insights
Nebulized teicoplanin significantly increased lung concentrations compared to intravenous delivery in a rat model. This aerosol administration shows promise for treating ventilator-associated pneumonia (VAP) caused by Staphylococcus aureus.
Area of Science:
- Pharmacology
- Pulmonary Medicine
- Infectious Diseases
Background:
- Ventilator-associated pneumonia (VAP) is a critical concern in mechanically ventilated patients, often caused by methicillin-resistant Staphylococcus aureus.
- Intravenous (IV) teicoplanin may not achieve optimal lung tissue concentrations.
- Aerosolized delivery of antibiotics is being explored as an alternative administration route.
Purpose of the Study:
- To compare lung and serum teicoplanin concentrations following aerosol nebulization versus IV administration.
- To evaluate the efficacy of aerosolized teicoplanin in a rat model for potential VAP treatment.
Main Methods:
- Eighty male Sprague-Dawley rats received a single dose of teicoplanin via IV or aerosol route.
- Lung and serum samples were collected post-sacrifice for teicoplanin concentration measurement using fluorescence polarization.
- Pharmacokinetic parameters including AUC/MIC, AUC, absorbed fraction, MRT, and MAT were calculated.
Main Results:
- Mean lung tissue teicoplanin concentrations were significantly higher in the aerosol group (1.94±1.33 mg/g at 15 min) compared to the IV group (0.04±0.01 mg/g).
- The mean lung AUC was 84 times greater after aerosol administration (67.4 mg hr(-1)g(-1)) than IV administration (0.8 mg hr(-1)g(-1)).
- Mean absorption time (MAT) and mean residence time (MRT) were prolonged with aerosol delivery.
Conclusions:
- Aerosolized teicoplanin achieved significantly higher lung tissue concentrations than IV administration in a rat model.
- The AUClung/MIC ratio met the target for eradicating Staphylococcus aureus with aerosolized teicoplanin.
- Nebulized teicoplanin presents a potential new therapeutic strategy for managing VAP.
