OBJECTIVE: To measure tissue pharmacokinetics of trovafloxacin (CP 99,219) in normal and infected animals by both direct tissue radioactivity measurements and positron emission tomography (PET). METHODS: Concentrations of [18F]trovafloxacin were measured in normal and infected rats (n=6/group), at 10, 30, 60, and 120 min after injection, by radioactivity measurements. In normal rabbits (n=4) and rabbits with Escherichia coli thigh infection (n=4), tissue concentrations of drug were measured over 2 h with PET. After acquiring the final images, the rabbits were killed and tissue concentrations measured with PET were compared to the results of direct tissue radioactivity measurements. RESULTS: In both species, there was rapid distribution of [18F] trovafloxacin in most peripheral organs. Peak concentrations of more than five times the MIC90 of most Enterobacteriaceae and anaerobes (>100-fold for most organisms) were achieved in all tissues and remained above this level for >2 h. Particularly high peak concentrations were achieved in the kidney (>75 micro g/g), liver (>100 micro g/g), blood (>40 micro g/g), and lung (>10 micro g/g). Even though the concentration of trovafloxacin in infected muscle was reduced (p<0.01), the peak concentration was still >4 micro g/g and tissue levels remained above 2 micro g/g for more than 2 h. Due to the lower concentrations that were achieved in the brain (peak approximately 5 micro g/g), it is expected that trovafloxacin will have limited central nervous system toxicity. CONCLUSION: PET with [18F]trovafloxacin is a useful technique for non-invasive measurements of tissue pharmacokinetics.
OBJECTIVE: To measure tissue pharmacokinetics of trovafloxacin (CP 99,219) in normal and infected animals by both direct tissue radioactivity measurements and positron emission tomography (PET). METHODS: Concentrations of [18F]trovafloxacin were measured in normal and infected rats (n=6/group), at 10, 30, 60, and 120 min after injection, by radioactivity measurements. In normal rabbits (n=4) and rabbits with Escherichia coli thigh infection (n=4), tissue concentrations of drug were measured over 2 h with PET. After acquiring the final images, the rabbits were killed and tissue concentrations measured with PET were compared to the results of direct tissue radioactivity measurements. RESULTS: In both species, there was rapid distribution of [18F] trovafloxacin in most peripheral organs. Peak concentrations of more than five times the MIC90 of most Enterobacteriaceae and anaerobes (>100-fold for most organisms) were achieved in all tissues and remained above this level for >2 h. Particularly high peak concentrations were achieved in the kidney (>75 micro g/g), liver (>100 micro g/g), blood (>40 micro g/g), and lung (>10 micro g/g). Even though the concentration of trovafloxacin in infected muscle was reduced (p<0.01), the peak concentration was still >4 micro g/g and tissue levels remained above 2 micro g/g for more than 2 h. Due to the lower concentrations that were achieved in the brain (peak approximately 5 micro g/g), it is expected that trovafloxacin will have limited central nervous system toxicity. CONCLUSION: PET with [18F]trovafloxacin is a useful technique for non-invasive measurements of tissue pharmacokinetics.
Authors: I Katsarolis; A Pefanis; D Iliopoulos; P Siaperas; P Karayiannakos; H Giamarellou Journal: Antimicrob Agents Chemother Date: 2000-09 Impact factor: 5.191
Authors: A J Fischman; J W Babich; A A Bonab; N M Alpert; J Vincent; R J Callahan; J A Correia; R H Rubin Journal: Antimicrob Agents Chemother Date: 1998-08 Impact factor: 5.191
Authors: Filipa Mota; Alvaro A Ordonez; George Firth; Camilo A Ruiz-Bedoya; Michelle T Ma; Sanjay K Jain Journal: J Med Chem Date: 2020-02-21 Impact factor: 7.446