Ca. Cox et al., Intratracheal administration of perfluorochemical-gentamicin suspension: Acomparison to intravenous administration in normal and injured lungs, PEDIAT PULM, 32(2), 2001, pp. 142-151
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.