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

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.

[1]  R. Gibson,et al.  Efficacy of aerosolized tobramycin in patients with cystic fibrosis. , 1993, The New England journal of medicine.

[2]  D. Touw,et al.  Pharmacokinetics of aerosolized tobramycin in adult patients with cystic fibrosis , 1997, Antimicrobial agents and chemotherapy.

[3]  J. Davis,et al.  Pharmacologic interactions of exogenous lung surfactant and recombinant human Cu/Zn superoxide dismutase. , 1994, Pediatric research.

[4]  E. Davies,et al.  The quantitative distribution of nebulized antibiotic in the lung in cystic fibrosis. , 1994, Respiratory medicine.

[5]  C. Langston,et al.  Exogenous surfactant enhances the delivery of recombinant adenoviral vectors to the lung. , 1997, Human gene therapy.

[6]  S. Fiel,et al.  Absolute Bioavailability and Absorption Characteristics of Aerosolized Tobramycin in Adults with Cystic Fibrosis , 1994, Journal of clinical pharmacology.

[7]  D. Gommers,et al.  Exogenous pulmonary surfactant as a drug delivering agent: influence of antibiotics on surfactant activity , 1996, British journal of pharmacology.

[8]  S. Groth,et al.  Binding and diffusion characteristics of 14C EDTA and 99mTc DTPA in respiratory tract mucus glycoprotein from patients with chronic bronchitis. , 1988, Thorax.

[9]  J. van den Hoff,et al.  A compartmental model for alveolar clearance of pertechnegas. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[10]  D. Gommers,et al.  Is it rational to treat pneumonia with exogenous surfactant? , 1993, The European respiratory journal.

[11]  R. Pauwels,et al.  The penetration of aminoglycosides into the alveolar lining fluid of rats. The effect of airway inflammation. , 1990, The American review of respiratory disease.

[12]  M. Fujimura,et al.  Bronchoalveolar lavage cell analysis in measles viral pneumonia. , 1993, The European respiratory journal.

[13]  H. Black,et al.  Aspects of the pharmacology and toxicology of tobramycin in animals and humans. , 1976, The Journal of infectious diseases.

[14]  D. Gommers,et al.  Rationale for Surfactant Therapy in Pneumonia , 1997 .

[15]  G. Coates,et al.  Effect of inspiratory resistance and PEEP on 99mTc-DTPA clearance. , 1986, Journal of applied physiology.

[16]  J. Fredberg,et al.  Pulmonary surfactant as a vehicle for intratracheal delivery of technetium sulfur colloid and pentamidine in hamster lungs. , 1991, The American review of respiratory disease.

[17]  U. Pipkorn,et al.  Clearance of 99mTc DTPA from guinea pig nasal, tracheobronchial, and bronchoalveolar airways. , 1990, Thorax.

[18]  D. Gommers,et al.  Pulmonary surfactant as vehicle for intratracheally instilled tobramycin in mice infected with Klebsiella pneumoniae , 1996, British journal of pharmacology.

[19]  G. Smaldone,et al.  Quantitative deposition of aerosolized gentamicin in cystic fibrosis. , 1987, The American review of respiratory disease.

[20]  K. Hisatake,et al.  Determination of surface‐spin orientations of rare‐earth iron garnet films by depth‐selective Mössbauer spectroscopy , 1986 .

[21]  M. Hodson,et al.  Inhalation of antibiotics in cystic fibrosis. , 1995, The European respiratory journal.

[22]  S. H. Al-Kouraishi.  Labelling and quality control of gentamycin with99mTc and biodistribution , 1988 .

[23]  A. Larsson,et al.  Exogenous surfactant therapy increases static lung compliance, and cannot be assessed by measurements of dynamic compliance alone , 1993, Critical care medicine.

[24]  D. Gommers,et al.  Influence of pulmonary surfactant on in vitro bactericidal activities of amoxicillin, ceftazidime, and tobramycin , 1995, Antimicrobial agents and chemotherapy.