A comparison of intratracheal and intravenous administration of gentamicin during liquid ventilation.
Pulmonary absorption of aminoglycosides is poor with intravenous administration, but may be enhanced by direct intratracheal administration of these drugs using perfluorochemical liquid ventilation (LV). To test this hypothesis, gentamicin sulfate was administered to two groups of newborn lambs during LV. Serum and lung tissue levels of gentamicin were compared after either pulmonary intratracheal (IT) or intravenous (IV) routes of administration. Serial serum levels of gentamicin were obtained every 15 min for the 1st h, every 30 min for the 2nd h, and then hourly until sacrifice (maximum 6 h). At sacrifice, representative samples of each lung lobe were homogenized and analyzed for tissue gentamicin content. At 1 h, serum gentamicin levels were similar in both groups: IT administration levels were 3.7 +/- 0.55 SE micrograms/ml and IV levels were 3.5 +/- 0.85 SE micrograms/ml. The peak serum gentamicin level of 4.8 +/- 0.8 SE micrograms/ml for the pulmonary administration group occurred 1.5 h after administration. Lung tissue levels of gentamicin for IT administration (4.04 +/- 0.62 SE micrograms/g) were significantly greater than for IV administration (1.75 +/- 0.33 SE micrograms/g; P < 0.05). There were no significant differences in interlobar gentamicin distribution for either mode of administration.


CONCLUSIONS
Perfluorochemical can be used as a vehicle for intratracheal delivery of antimicrobials. This route provides equivalent serum levels at 1 h, higher lung tissue levels, and uniform interlobar distribution relative to intravenous administration of gentamicin. We speculate that pulmonary administered gentamicin during LV may provide an effective alternative treatment modality in the management of severe neonatal pneumonia.
Zelinka
M A
MA
Department of Physiology and Paediatrics, Temple University School of Medicine, Philadelphia, USA.
Wolfson
M R
MR
Calligaro
I
I
Rubenstein
S D
SD
Greenspan
J S
JS
Shaffer
T H
TH
D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000592:standards*; D005466:Fluorocarbons / Q000008:administration & dosage*; D005839:Gentamicins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007275:Injections, Intravenous / Q000592:standards; D007442:Intubation, Intratracheal; D008168:Lung / Q000737:chemistry; D011897:Random Allocation; D012121:Respiration, Artificial / Q000379:methods*; D012756:Sheep
D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D005466:Fluorocarbons; D005839:Gentamicins; C008805:perfluorodecalin