Lung clearance of intratracheally instilled 99mTc‐tobramycin using pulmonary surfactant as vehicle

• Published in: British journal of pharmacology Vol. 126; no. 5; pp. 1091 - 1096
• Main Authors: Van 't Veen, Annemarie, Gommers, Diederik, Verbrugge, Serge J C, Wollmer, Per, Mouton, Johan W, Kooij, Peter P M, Lachmann, Burkhard
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-03-1999; Nature Publishing
• Subjects: 99mTc‐tobramycin; Administration, Inhalation; Animals; Anti-Bacterial Agents - pharmacokinetics; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; local antimicrobial therapy; Lung - metabolism; lung clearance; Male; Medical sciences; Metabolic Clearance Rate; Pharmacology. Drug treatments; Pulmonary surfactant; Pulmonary Surfactants - pharmacology; Radiopharmaceuticals - pharmacokinetics; Rats; Rats, Sprague-Dawley; surfactant as carrier; Technetium Compounds - metabolism; Tobramycin - pharmacokinetics; Rat; Lung; Rodentia; Clearance; Surfactant; Respiratory system; Vertebrata; Antibiotic; Mammalia; Aminoglycoside; Animal; Adjuvant; Tobramycin; Antibacterial agent; Pharmacokinetics; Intratracheal administration
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0702405

The use of pulmonary exogenous surfactant as a vehicle for intratracheally administered antibiotics to improve local antimicrobial therapy has been proposed. The present study investigated lung clearance rates in the rat of intratracheally instilled technetium labelled tobramycin with and without the addition of surfactant to the antibiotic solution.
The influence of surfactant on 99mTc‐tobramycin lung clearance rates was studied dynamically with a gamma‐camera in anaesthetized spontaneously breathing animals and in mechanically ventilated animals.
The results show that instillation of 99mTc‐tobramycin with use of surfactant as vehicle significantly increases 99mTc‐tobramycin lung clearance compared to instillation of 99mTc‐tobramycin solution alone (P=0.006 between the two spontaneously breathing groups of animals and P=0.02 between the two ventilated groups of animals, ANOVA for repeated time measurements). The half life (t½) of composite clearance curves in spontaneous breathing animals was 147 min for animals receiving 99mTc‐tobramycin versus 61 min for animals receiving 99mTc‐tobramycin with surfactant. In mechanically ventilated animals this was 163 min versus 51 min, respectively.
It is concluded that exogenous surfactant, used as vehicle for intratracheally instilled 99mTc‐tobramycin, increases lung clearance rate of 99mTc‐tobramycin in rats.
British Journal of Pharmacology (1999) 126, 1091–1096; doi:10.1038/sj.bjp.0702405