Intratracheal administration of perfluorochemical-gentamicin suspension: Acomparison to intravenous administration in normal and injured lungs

Respiratory infections can lead to acute lung injury and perfusion abnormal ities. We hypothesized that intratracheal (IT) administration of a perfluor ochemical (PFC) gentamicin (G) suspension as compared to intravenous (IV) a dministration of gentamicin will result in higher lung tissue levels of gen tamicin, while maintaining safe serum levels. To test this hypothesis, 21 l ambs with normal and acid injured lungs were studied for 4 hr, using 2 diff erent drug delivery methods, IT and IV. Lungs were injured with warm HCl ac id in saline lavage, followed by partial liquid ventilation with perflubron (bolus FRC = 20 mL/kg). G at a dose of 5 mg/kg was delivered either IT (G- PFC; 20 mL/kg) or IV (aqueous injection with IT 20 mL/kg PFC alone). Throug hout the study, serum G levels, arterial blood gases, respiratory system co mpliance, and mean arterial blood pressure were measured. Lung tissue G lev els were measured at 4 hr and averaged across lobes. Physiologic gas exchan ge and pulmonary function were maintained throughout the protocol for both the normal and injured lungs. Intravenously administered G resulted in an initial 5-min serum concentrati on of 43 +/- 2.5 mcg/ mL, followed by an exponential decline over the 4-hr protocol to a level of 2.1 +/- 0.23 mcg/mL at hr 4. The intratracheally adm inistered G suspension resulted in a 5-min serum concentration of 1.8 +/- 0 .98 mcg/mL and remained relatively constant throughout the protocol, with a 4-hr level of 1.6 +/- 0.29 mcg/mL. With respect to lung tissue G levels, I T administration was significantly more effective in delivering the drug to the normal lungs than IV (31.4 +/- 3.3 mcg/g vs. 4.0 +/- 0.7 mcg/g) 4 hr a fter administration, In the lung injury group, there was a small but signif icant difference in lung tissue G levels, with the IT-administered perfluor ochemical-G suspension achieving greater levels than the IV-administered G (11.9 +/- 0.52 mcg/g vs. 10.1 +/- 0.8 mcg/g). Additionally, the drug delive red IV and IT in both the normal and injured lung models was homogeneously distributed throughout the lung. These data show that G lung tissue levels in both normal and injured lungs were higher in the IT group when compared to IV administration. The results of this study demonstrate that in normal and injured lungs, homogeneous G lung tissue levels can be more effectively achieved at lower serum levels w hen delivered IT in a G-PFC suspension as compared to IV administration. (C ) 2001 Wiley-Liss, Inc.