The Experts below are selected from a list of 693 Experts worldwide ranked by ideXlab platform

Roy Cleeland - One of the best experts on this subject based on the ideXlab platform.

  • pharmacokinetics of 18f Fleroxacin in patients with acute exacerbations of chronic bronchitis and complicated urinary tract infection studied by positron emission tomography
    Antimicrobial Agents and Chemotherapy, 1996
    Co-Authors: Alan J Fischman, Eli Livni, John W Babich, Nathaniel M Alpert, Ali A Bonab, S Chodosh, Francis J Mcgovern, P Kamitsuka, Yuying Liu, Roy Cleeland
    Abstract:

    The pharmacokinetics of Fleroxacin, a new broad-spectrum fluoroquinolone, were measured by positron emission tomography (PET) with [18F]Fleroxacin in five patients with acute bacterial exacerbations of chronic bronchitis and in five patients with symptomatic, complicated urinary tract infection. Two studies were performed with each patient, one within 24 h of the initiation and one within 24 h of the completion of a 7-day course of Fleroxacin, 400 mg/day. For each study, the patient received an infusion of that day's therapeutic dose of Fleroxacin (400 mg) supplemented with approximately 740 MBq of [18F]Fleroxacin, and serial PET images and blood samples were collected for 6 to 8 h starting at the initiation of the infusion. Between studies, the drug was administered orally. In all infected tissues, there was rapid accumulation of radiolabeled drug, with stable levels achieved within 1 h after completion of the infusion. In kidneys, accumulation was greater in the presence of active infection (P 30 micrograms/g), prostate glands (> 11 micrograms/g), and lungs (> 14 micrograms/g). Plateau concentrations (2 to 8 h; given as mean micrograms per gram +/- standard error of the mean) of drug in kidneys (15.11 +/- 0.55), prostate glands (5.08 +/- 0.19), and lungs (5.75 +/- 0.22) were also well above the MIC90 for most relevant pathogens. All patients had a good therapeutic response to Fleroxacin.

  • tissue pharmacokinetics of Fleroxacin in humans as determined by positron emission tomography
    International Journal of Antimicrobial Agents, 1994
    Co-Authors: Barbara Prosser, Roy Cleeland, Eli Livni, John W Babich, Nathaniel M Alpert, Yuying Liu, E Thom, Robert H Rubin, Alan J Fischman
    Abstract:

    Abstract The delivery of Fleroxacin, a new broad-spectrum fluoroquinolone, to the major organs of the body was studied in 12 normal human volunteers (nine men and three women), utilizing positron emission tomography (PET). Following the infusion of 20 mCi of [ 18 F]Fleroxacin in conjuction with a standard therapeutic dose of 400 mg, images were acquired over 8 h. Beginning the next day, the subjects received unlabeled drug at a dose of 400 mg/day for 3 days, with a repeat PET study on the fifth day. Fleroxacin is distributed widely throughout the body, with the notable exception of the central nervous system, with stable levels achieved within 1 h after completion of the infusion. Especially high peak concentrations (⩾18 μ g/g) were achieved in the kidney, liver, lung myocardium, and spleen. The mean plateau concentrations (2–8 h post-infusion, μg/g) were: brain 0.83; myocardium, 4.53; lung, 5.80, liver, 7.31; spleen, 6.00; bowel, 3.53; kidney, 8.85; bone, 2.87; muscle, 4.60; prostate, 4.65; uterus, 3.87; breast, 2.68; and blood, 2.35. Repetitive dosing had no significant effect on the pharmacokinetics of the drug. Since the MIC 90 's of the family Enterobacterioaceae and Neisseria gonorrhoeae are μ g/ml, with the great majority of the individual species ⩾1 μ g/ml, these results suggest that a single daily dose of 400 mg of Fleroxacin should be effective in the treatment of infections such as urinary tract infection and gonorrhea.

  • Comparative evaluation of Fleroxacin, ampicillin, trimethoprimsulfamethoxazole, and gentamicin as treatments of catheter-associated urinary tract infection in a rabbit model
    International Journal of Antimicrobial Agents, 1994
    Co-Authors: Douglas W Morck, M E Olson, S G Mckay, Kan Lam, Barbara Prosser, Roy Cleeland, B. D. Ellis, J W Costerton
    Abstract:

    Fleroxacin, ampicillin, trimethoprim-sulfamethoxazole, and gentamicin were comparatively evaluated for effectiveness in treating experimentally induced catheter-associated urinary tract infection and bacteriuria in a rabbit model with a closed drainage system. Fleroxacin, ampicillin and gentamicin effectively eliminated a lactose-negative, streptomycin-resistant uropathogenic strain of Escherichia coli (WE6933) from bag urine and catheter port urine, while trimethoprim-sulfamethoxazole only marginally reduced urine bacterial counts when compared to rabbits that received no antibiotic therapy. Fleroxacin eliminated E. coli from the catheter surfaces and from tissues adjacent to the catheter. Ampicillin or gentamicin therapy also eliminated biofilm bacteria from the catheter surfaces, but did not eliminate th residual bacteria from tissue adjacent to the septic catheters despite achieving urine levels of antibiotics substantially higher than minimum bactericidal concentrations for this pathogen. Trimethoprim-sulfamethoxazole was ineffective in eliminating E. coli from the catheter surfaces and the adjacent tissues. The ability of Fleroxacin to effectively eliminate biofilm bacteria from catheter surfaces and tissues adjacent to such medical devices in the urinary tract may prove useful in the treatment of catheter-associated urinary tract infection and bacteriuria in mammals and humans.

  • pharmacokinetics of 18f Fleroxacin in healthy human subjects studied by using positron emission tomography
    Antimicrobial Agents and Chemotherapy, 1993
    Co-Authors: Alan J Fischman, Barbara Prosser, Roy Cleeland, Eli Livni, John W Babich, Nathaniel M Alpert, Yuying Liu, E Thom, J A Correia, H W Strauss
    Abstract:

    Positron emission tomography (PET) with [18F]Fleroxacin was used to study the pharmacokinetics of Fleroxacin, a new broad-spectrum fluoroquinolone, in 12 healthy volunteers (9 men and 3 women). The subjects were infused with a standard therapeutic dose of Fleroxacin (400 mg) supplemented with approximately 20 mCi of [18F]Fleroxacin. Serial PET images were made and blood samples were collected for 8 h, starting at the initiation of the infusion. The subjects were then treated with unlabeled drug for 3 days (400 mg/day). On the fifth day, infusion of radiolabeled drug, PET imaging, and blood collection were repeated. In most organs, there was rapid accumulation of radiolabeled drug, with stable levels achieved within 1 h after completion of the infusion. Especially high peak concentrations (in micrograms per gram) were achieved in the kidney (> 34), liver (> 25), lung (> 20), myocardium (> 19), and spleen (> 18). Peak concentrations of drug more than two times the MIC for 90% of Enterobacteriaceae strains tested (> 10-fold for most organisms) were achieved in all tissues except the brain and remained above this level for more than 6 to 8 h. The plateau concentrations in tissues (2 to 8 h, in micrograms per gram +/- standard error of the mean) of drug were as follows: brain, 0.83 +/- 0.032; myocardium, 4.53 +/- 0.24; lung, 5.80 +/- 0.48; liver, 7.31 +/- 0.33; spleen, 6.00 +/- 0.47; bowel, 3.53 +/- 0.74; kidney, 8.85 +/- 0.64; bone, 2.87 +/- 0.29; muscle, 4.60 +/- 0.33; prostate, 4.65 +/- 0.48; uterus, 3.87 +/- 0.39; breast, 2.68 +/- 0.11; and blood, 2.35 +/- 0.09. Concentrations of Fleroxacin in tissue were similar in males and females, before and after pretreatment with unlabeled drug.

  • therapeutic efficacy of Fleroxacin for eliminating catheter associated urinary tract infection in a rabbit model
    The American Journal of Medicine, 1993
    Co-Authors: Douglas W Morck, M E Olson, S G Mckay, Kan Lam, Barbara Prosser, Roy Cleeland, J W Costerton
    Abstract:

    The efficacy of Fleroxacin as therapy for experimentally induced catheter-associated urinary tract infection (CAUTI) was examined. A rabbit model of CAUTI using a closed urinary catheter drainage system and the mutant strain of Escherichia coli (WE 6933) were used to examine three dosage regimens (30 mg/kg q8h i.v.; 20 mg/kg q8h i.v.; and 10 mg/kg q8h++i.v.) of Fleroxacin administered intravenously for 4 days. Quantitative bacterial counts, urinary concentrations of Fleroxacin and desmethylferoxacin, histopathologic changes, and electron microscopic evaluation of catheter-associated biofilm and mucosal biofilm were performed. The results indicated that the bacterial biofilm on the urinary catheter could be eliminated by Fleroxacin at 30 mg/kg q8h i.v. and 20 mg/kg q8h i.v. Fleroxacin concentrations in urine exceeded the levels necessary to destroy E. coli. Viable bacteria were eliminated with the third regimen (10 mg/kg q8h i.v.), but electron microscopy demonstrated remnants of bacterial biofilm. Histopathologic changes were significantly reduced in all Fleroxacin-treated rabbits, and scanning electron microscopy showed deterioration of the bacterial biofilm on the surface of the Foley catheter in treated animals. These data suggest that Fleroxacin may be useful for treating catheter-related infections because these therapeutic dosages limited ascending infections of the urethra and bladder, eliminated catheter-associated biofilms, and killed planktonic bacteria in urine.

Alan J Fischman - One of the best experts on this subject based on the ideXlab platform.

  • pharmacokinetics of 18f Fleroxacin in patients with acute exacerbations of chronic bronchitis and complicated urinary tract infection studied by positron emission tomography
    Antimicrobial Agents and Chemotherapy, 1996
    Co-Authors: Alan J Fischman, Eli Livni, John W Babich, Nathaniel M Alpert, Ali A Bonab, S Chodosh, Francis J Mcgovern, P Kamitsuka, Yuying Liu, Roy Cleeland
    Abstract:

    The pharmacokinetics of Fleroxacin, a new broad-spectrum fluoroquinolone, were measured by positron emission tomography (PET) with [18F]Fleroxacin in five patients with acute bacterial exacerbations of chronic bronchitis and in five patients with symptomatic, complicated urinary tract infection. Two studies were performed with each patient, one within 24 h of the initiation and one within 24 h of the completion of a 7-day course of Fleroxacin, 400 mg/day. For each study, the patient received an infusion of that day's therapeutic dose of Fleroxacin (400 mg) supplemented with approximately 740 MBq of [18F]Fleroxacin, and serial PET images and blood samples were collected for 6 to 8 h starting at the initiation of the infusion. Between studies, the drug was administered orally. In all infected tissues, there was rapid accumulation of radiolabeled drug, with stable levels achieved within 1 h after completion of the infusion. In kidneys, accumulation was greater in the presence of active infection (P 30 micrograms/g), prostate glands (> 11 micrograms/g), and lungs (> 14 micrograms/g). Plateau concentrations (2 to 8 h; given as mean micrograms per gram +/- standard error of the mean) of drug in kidneys (15.11 +/- 0.55), prostate glands (5.08 +/- 0.19), and lungs (5.75 +/- 0.22) were also well above the MIC90 for most relevant pathogens. All patients had a good therapeutic response to Fleroxacin.

  • tissue pharmacokinetics of Fleroxacin in humans as determined by positron emission tomography
    International Journal of Antimicrobial Agents, 1994
    Co-Authors: Barbara Prosser, Roy Cleeland, Eli Livni, John W Babich, Nathaniel M Alpert, Yuying Liu, E Thom, Robert H Rubin, Alan J Fischman
    Abstract:

    Abstract The delivery of Fleroxacin, a new broad-spectrum fluoroquinolone, to the major organs of the body was studied in 12 normal human volunteers (nine men and three women), utilizing positron emission tomography (PET). Following the infusion of 20 mCi of [ 18 F]Fleroxacin in conjuction with a standard therapeutic dose of 400 mg, images were acquired over 8 h. Beginning the next day, the subjects received unlabeled drug at a dose of 400 mg/day for 3 days, with a repeat PET study on the fifth day. Fleroxacin is distributed widely throughout the body, with the notable exception of the central nervous system, with stable levels achieved within 1 h after completion of the infusion. Especially high peak concentrations (⩾18 μ g/g) were achieved in the kidney, liver, lung myocardium, and spleen. The mean plateau concentrations (2–8 h post-infusion, μg/g) were: brain 0.83; myocardium, 4.53; lung, 5.80, liver, 7.31; spleen, 6.00; bowel, 3.53; kidney, 8.85; bone, 2.87; muscle, 4.60; prostate, 4.65; uterus, 3.87; breast, 2.68; and blood, 2.35. Repetitive dosing had no significant effect on the pharmacokinetics of the drug. Since the MIC 90 's of the family Enterobacterioaceae and Neisseria gonorrhoeae are μ g/ml, with the great majority of the individual species ⩾1 μ g/ml, these results suggest that a single daily dose of 400 mg of Fleroxacin should be effective in the treatment of infections such as urinary tract infection and gonorrhea.

  • pharmacokinetics of 18f Fleroxacin in healthy human subjects studied by using positron emission tomography
    Antimicrobial Agents and Chemotherapy, 1993
    Co-Authors: Alan J Fischman, Barbara Prosser, Roy Cleeland, Eli Livni, John W Babich, Nathaniel M Alpert, Yuying Liu, E Thom, J A Correia, H W Strauss
    Abstract:

    Positron emission tomography (PET) with [18F]Fleroxacin was used to study the pharmacokinetics of Fleroxacin, a new broad-spectrum fluoroquinolone, in 12 healthy volunteers (9 men and 3 women). The subjects were infused with a standard therapeutic dose of Fleroxacin (400 mg) supplemented with approximately 20 mCi of [18F]Fleroxacin. Serial PET images were made and blood samples were collected for 8 h, starting at the initiation of the infusion. The subjects were then treated with unlabeled drug for 3 days (400 mg/day). On the fifth day, infusion of radiolabeled drug, PET imaging, and blood collection were repeated. In most organs, there was rapid accumulation of radiolabeled drug, with stable levels achieved within 1 h after completion of the infusion. Especially high peak concentrations (in micrograms per gram) were achieved in the kidney (> 34), liver (> 25), lung (> 20), myocardium (> 19), and spleen (> 18). Peak concentrations of drug more than two times the MIC for 90% of Enterobacteriaceae strains tested (> 10-fold for most organisms) were achieved in all tissues except the brain and remained above this level for more than 6 to 8 h. The plateau concentrations in tissues (2 to 8 h, in micrograms per gram +/- standard error of the mean) of drug were as follows: brain, 0.83 +/- 0.032; myocardium, 4.53 +/- 0.24; lung, 5.80 +/- 0.48; liver, 7.31 +/- 0.33; spleen, 6.00 +/- 0.47; bowel, 3.53 +/- 0.74; kidney, 8.85 +/- 0.64; bone, 2.87 +/- 0.29; muscle, 4.60 +/- 0.33; prostate, 4.65 +/- 0.48; uterus, 3.87 +/- 0.39; breast, 2.68 +/- 0.11; and blood, 2.35 +/- 0.09. Concentrations of Fleroxacin in tissue were similar in males and females, before and after pretreatment with unlabeled drug.

  • pharmacokinetics of 18f labeled Fleroxacin in rabbits with escherichia coli infections studied with positron emission tomography
    Antimicrobial Agents and Chemotherapy, 1992
    Co-Authors: Alan J Fischman, Barbara Prosser, Roy Cleeland, Eli Livni, John W Babich, Nathaniel M Alpert, Yuying Liu, E Thom, Ronald J Callahan, J A Correia
    Abstract:

    18F-labeled Fleroxacin was used to measure the pharmacokinetics of Fleroxacin in healthy and infected animals by positron emission tomography (PET) and tissue radioactivity measurements. In all experiments, a pharmacological dose of unlabeled drug (10 mg/kg) was coinjected with the tracer. The pharmacokinetics of [18F]Fleroxacin was measured in groups of healthy mice (n = six per group) at 10, 30, 60, and 120 min after injection and in groups of rats with Escherichia coli thigh infections (n = six per group) at 60 and 120 min after injection by radioactivity measurements in excised tissues. In healthy rabbits (n = 4) and in rabbits with E. coli thigh infections (n = 4), tissue concentrations of drug were determined by serial PET imaging over 2 h; after the final image was acquired, animals were sacrificed and concentrations measured by PET were compared with the results of tissue radioactivity measurements. In all three species, there was rapid equilibration of [18F]Fleroxacin to significant concentrations in most peripheral organs; low concentrations of drug were detected in the brain. Accumulations of radiolabeled drug in infected and healthy thigh muscles were similar. Peak concentrations of drug of more than three times the MIC for 90% of members of the family Enterobacteriaceae (greater than 100-fold for most organisms) were achieved in all tissues except brain and remained above this level for more than 2 h. Especially high peak concentrations were achieved in the kidney (greater than 75 micrograms/g), liver (greater than 50 micrograms/g), blood (greater than 25 micrograms/g), and bone and lung (greater than 10 micrograms/g). Since the MICs for 90% of all Enterobacteriaceae are <2 micrograms/ml, Fleroxacin should be particularly useful in treating gram-negative infections affecting these tissues. In contrast, the low concentration of drug delivered to the brain should limit the toxicity of the drug for the central nervous system.

Barbara Prosser - One of the best experts on this subject based on the ideXlab platform.

  • tissue pharmacokinetics of Fleroxacin in humans as determined by positron emission tomography
    International Journal of Antimicrobial Agents, 1994
    Co-Authors: Barbara Prosser, Roy Cleeland, Eli Livni, John W Babich, Nathaniel M Alpert, Yuying Liu, E Thom, Robert H Rubin, Alan J Fischman
    Abstract:

    Abstract The delivery of Fleroxacin, a new broad-spectrum fluoroquinolone, to the major organs of the body was studied in 12 normal human volunteers (nine men and three women), utilizing positron emission tomography (PET). Following the infusion of 20 mCi of [ 18 F]Fleroxacin in conjuction with a standard therapeutic dose of 400 mg, images were acquired over 8 h. Beginning the next day, the subjects received unlabeled drug at a dose of 400 mg/day for 3 days, with a repeat PET study on the fifth day. Fleroxacin is distributed widely throughout the body, with the notable exception of the central nervous system, with stable levels achieved within 1 h after completion of the infusion. Especially high peak concentrations (⩾18 μ g/g) were achieved in the kidney, liver, lung myocardium, and spleen. The mean plateau concentrations (2–8 h post-infusion, μg/g) were: brain 0.83; myocardium, 4.53; lung, 5.80, liver, 7.31; spleen, 6.00; bowel, 3.53; kidney, 8.85; bone, 2.87; muscle, 4.60; prostate, 4.65; uterus, 3.87; breast, 2.68; and blood, 2.35. Repetitive dosing had no significant effect on the pharmacokinetics of the drug. Since the MIC 90 's of the family Enterobacterioaceae and Neisseria gonorrhoeae are μ g/ml, with the great majority of the individual species ⩾1 μ g/ml, these results suggest that a single daily dose of 400 mg of Fleroxacin should be effective in the treatment of infections such as urinary tract infection and gonorrhea.

  • Comparative evaluation of Fleroxacin, ampicillin, trimethoprimsulfamethoxazole, and gentamicin as treatments of catheter-associated urinary tract infection in a rabbit model
    International Journal of Antimicrobial Agents, 1994
    Co-Authors: Douglas W Morck, M E Olson, S G Mckay, Kan Lam, Barbara Prosser, Roy Cleeland, B. D. Ellis, J W Costerton
    Abstract:

    Fleroxacin, ampicillin, trimethoprim-sulfamethoxazole, and gentamicin were comparatively evaluated for effectiveness in treating experimentally induced catheter-associated urinary tract infection and bacteriuria in a rabbit model with a closed drainage system. Fleroxacin, ampicillin and gentamicin effectively eliminated a lactose-negative, streptomycin-resistant uropathogenic strain of Escherichia coli (WE6933) from bag urine and catheter port urine, while trimethoprim-sulfamethoxazole only marginally reduced urine bacterial counts when compared to rabbits that received no antibiotic therapy. Fleroxacin eliminated E. coli from the catheter surfaces and from tissues adjacent to the catheter. Ampicillin or gentamicin therapy also eliminated biofilm bacteria from the catheter surfaces, but did not eliminate th residual bacteria from tissue adjacent to the septic catheters despite achieving urine levels of antibiotics substantially higher than minimum bactericidal concentrations for this pathogen. Trimethoprim-sulfamethoxazole was ineffective in eliminating E. coli from the catheter surfaces and the adjacent tissues. The ability of Fleroxacin to effectively eliminate biofilm bacteria from catheter surfaces and tissues adjacent to such medical devices in the urinary tract may prove useful in the treatment of catheter-associated urinary tract infection and bacteriuria in mammals and humans.

  • pharmacokinetics of 18f Fleroxacin in healthy human subjects studied by using positron emission tomography
    Antimicrobial Agents and Chemotherapy, 1993
    Co-Authors: Alan J Fischman, Barbara Prosser, Roy Cleeland, Eli Livni, John W Babich, Nathaniel M Alpert, Yuying Liu, E Thom, J A Correia, H W Strauss
    Abstract:

    Positron emission tomography (PET) with [18F]Fleroxacin was used to study the pharmacokinetics of Fleroxacin, a new broad-spectrum fluoroquinolone, in 12 healthy volunteers (9 men and 3 women). The subjects were infused with a standard therapeutic dose of Fleroxacin (400 mg) supplemented with approximately 20 mCi of [18F]Fleroxacin. Serial PET images were made and blood samples were collected for 8 h, starting at the initiation of the infusion. The subjects were then treated with unlabeled drug for 3 days (400 mg/day). On the fifth day, infusion of radiolabeled drug, PET imaging, and blood collection were repeated. In most organs, there was rapid accumulation of radiolabeled drug, with stable levels achieved within 1 h after completion of the infusion. Especially high peak concentrations (in micrograms per gram) were achieved in the kidney (> 34), liver (> 25), lung (> 20), myocardium (> 19), and spleen (> 18). Peak concentrations of drug more than two times the MIC for 90% of Enterobacteriaceae strains tested (> 10-fold for most organisms) were achieved in all tissues except the brain and remained above this level for more than 6 to 8 h. The plateau concentrations in tissues (2 to 8 h, in micrograms per gram +/- standard error of the mean) of drug were as follows: brain, 0.83 +/- 0.032; myocardium, 4.53 +/- 0.24; lung, 5.80 +/- 0.48; liver, 7.31 +/- 0.33; spleen, 6.00 +/- 0.47; bowel, 3.53 +/- 0.74; kidney, 8.85 +/- 0.64; bone, 2.87 +/- 0.29; muscle, 4.60 +/- 0.33; prostate, 4.65 +/- 0.48; uterus, 3.87 +/- 0.39; breast, 2.68 +/- 0.11; and blood, 2.35 +/- 0.09. Concentrations of Fleroxacin in tissue were similar in males and females, before and after pretreatment with unlabeled drug.

  • therapeutic efficacy of Fleroxacin for eliminating catheter associated urinary tract infection in a rabbit model
    The American Journal of Medicine, 1993
    Co-Authors: Douglas W Morck, M E Olson, S G Mckay, Kan Lam, Barbara Prosser, Roy Cleeland, J W Costerton
    Abstract:

    The efficacy of Fleroxacin as therapy for experimentally induced catheter-associated urinary tract infection (CAUTI) was examined. A rabbit model of CAUTI using a closed urinary catheter drainage system and the mutant strain of Escherichia coli (WE 6933) were used to examine three dosage regimens (30 mg/kg q8h i.v.; 20 mg/kg q8h i.v.; and 10 mg/kg q8h++i.v.) of Fleroxacin administered intravenously for 4 days. Quantitative bacterial counts, urinary concentrations of Fleroxacin and desmethylferoxacin, histopathologic changes, and electron microscopic evaluation of catheter-associated biofilm and mucosal biofilm were performed. The results indicated that the bacterial biofilm on the urinary catheter could be eliminated by Fleroxacin at 30 mg/kg q8h i.v. and 20 mg/kg q8h i.v. Fleroxacin concentrations in urine exceeded the levels necessary to destroy E. coli. Viable bacteria were eliminated with the third regimen (10 mg/kg q8h i.v.), but electron microscopy demonstrated remnants of bacterial biofilm. Histopathologic changes were significantly reduced in all Fleroxacin-treated rabbits, and scanning electron microscopy showed deterioration of the bacterial biofilm on the surface of the Foley catheter in treated animals. These data suggest that Fleroxacin may be useful for treating catheter-related infections because these therapeutic dosages limited ascending infections of the urethra and bladder, eliminated catheter-associated biofilms, and killed planktonic bacteria in urine.

  • pharmacokinetics of 18f labeled Fleroxacin in rabbits with escherichia coli infections studied with positron emission tomography
    Antimicrobial Agents and Chemotherapy, 1992
    Co-Authors: Alan J Fischman, Barbara Prosser, Roy Cleeland, Eli Livni, John W Babich, Nathaniel M Alpert, Yuying Liu, E Thom, Ronald J Callahan, J A Correia
    Abstract:

    18F-labeled Fleroxacin was used to measure the pharmacokinetics of Fleroxacin in healthy and infected animals by positron emission tomography (PET) and tissue radioactivity measurements. In all experiments, a pharmacological dose of unlabeled drug (10 mg/kg) was coinjected with the tracer. The pharmacokinetics of [18F]Fleroxacin was measured in groups of healthy mice (n = six per group) at 10, 30, 60, and 120 min after injection and in groups of rats with Escherichia coli thigh infections (n = six per group) at 60 and 120 min after injection by radioactivity measurements in excised tissues. In healthy rabbits (n = 4) and in rabbits with E. coli thigh infections (n = 4), tissue concentrations of drug were determined by serial PET imaging over 2 h; after the final image was acquired, animals were sacrificed and concentrations measured by PET were compared with the results of tissue radioactivity measurements. In all three species, there was rapid equilibration of [18F]Fleroxacin to significant concentrations in most peripheral organs; low concentrations of drug were detected in the brain. Accumulations of radiolabeled drug in infected and healthy thigh muscles were similar. Peak concentrations of drug of more than three times the MIC for 90% of members of the family Enterobacteriaceae (greater than 100-fold for most organisms) were achieved in all tissues except brain and remained above this level for more than 2 h. Especially high peak concentrations were achieved in the kidney (greater than 75 micrograms/g), liver (greater than 50 micrograms/g), blood (greater than 25 micrograms/g), and bone and lung (greater than 10 micrograms/g). Since the MICs for 90% of all Enterobacteriaceae are <2 micrograms/ml, Fleroxacin should be particularly useful in treating gram-negative infections affecting these tissues. In contrast, the low concentration of drug delivered to the brain should limit the toxicity of the drug for the central nervous system.

John W Babich - One of the best experts on this subject based on the ideXlab platform.

  • pharmacokinetics of 18f Fleroxacin in patients with acute exacerbations of chronic bronchitis and complicated urinary tract infection studied by positron emission tomography
    Antimicrobial Agents and Chemotherapy, 1996
    Co-Authors: Alan J Fischman, Eli Livni, John W Babich, Nathaniel M Alpert, Ali A Bonab, S Chodosh, Francis J Mcgovern, P Kamitsuka, Yuying Liu, Roy Cleeland
    Abstract:

    The pharmacokinetics of Fleroxacin, a new broad-spectrum fluoroquinolone, were measured by positron emission tomography (PET) with [18F]Fleroxacin in five patients with acute bacterial exacerbations of chronic bronchitis and in five patients with symptomatic, complicated urinary tract infection. Two studies were performed with each patient, one within 24 h of the initiation and one within 24 h of the completion of a 7-day course of Fleroxacin, 400 mg/day. For each study, the patient received an infusion of that day's therapeutic dose of Fleroxacin (400 mg) supplemented with approximately 740 MBq of [18F]Fleroxacin, and serial PET images and blood samples were collected for 6 to 8 h starting at the initiation of the infusion. Between studies, the drug was administered orally. In all infected tissues, there was rapid accumulation of radiolabeled drug, with stable levels achieved within 1 h after completion of the infusion. In kidneys, accumulation was greater in the presence of active infection (P 30 micrograms/g), prostate glands (> 11 micrograms/g), and lungs (> 14 micrograms/g). Plateau concentrations (2 to 8 h; given as mean micrograms per gram +/- standard error of the mean) of drug in kidneys (15.11 +/- 0.55), prostate glands (5.08 +/- 0.19), and lungs (5.75 +/- 0.22) were also well above the MIC90 for most relevant pathogens. All patients had a good therapeutic response to Fleroxacin.

  • tissue pharmacokinetics of Fleroxacin in humans as determined by positron emission tomography
    International Journal of Antimicrobial Agents, 1994
    Co-Authors: Barbara Prosser, Roy Cleeland, Eli Livni, John W Babich, Nathaniel M Alpert, Yuying Liu, E Thom, Robert H Rubin, Alan J Fischman
    Abstract:

    Abstract The delivery of Fleroxacin, a new broad-spectrum fluoroquinolone, to the major organs of the body was studied in 12 normal human volunteers (nine men and three women), utilizing positron emission tomography (PET). Following the infusion of 20 mCi of [ 18 F]Fleroxacin in conjuction with a standard therapeutic dose of 400 mg, images were acquired over 8 h. Beginning the next day, the subjects received unlabeled drug at a dose of 400 mg/day for 3 days, with a repeat PET study on the fifth day. Fleroxacin is distributed widely throughout the body, with the notable exception of the central nervous system, with stable levels achieved within 1 h after completion of the infusion. Especially high peak concentrations (⩾18 μ g/g) were achieved in the kidney, liver, lung myocardium, and spleen. The mean plateau concentrations (2–8 h post-infusion, μg/g) were: brain 0.83; myocardium, 4.53; lung, 5.80, liver, 7.31; spleen, 6.00; bowel, 3.53; kidney, 8.85; bone, 2.87; muscle, 4.60; prostate, 4.65; uterus, 3.87; breast, 2.68; and blood, 2.35. Repetitive dosing had no significant effect on the pharmacokinetics of the drug. Since the MIC 90 's of the family Enterobacterioaceae and Neisseria gonorrhoeae are μ g/ml, with the great majority of the individual species ⩾1 μ g/ml, these results suggest that a single daily dose of 400 mg of Fleroxacin should be effective in the treatment of infections such as urinary tract infection and gonorrhea.

  • pharmacokinetics of 18f Fleroxacin in healthy human subjects studied by using positron emission tomography
    Antimicrobial Agents and Chemotherapy, 1993
    Co-Authors: Alan J Fischman, Barbara Prosser, Roy Cleeland, Eli Livni, John W Babich, Nathaniel M Alpert, Yuying Liu, E Thom, J A Correia, H W Strauss
    Abstract:

    Positron emission tomography (PET) with [18F]Fleroxacin was used to study the pharmacokinetics of Fleroxacin, a new broad-spectrum fluoroquinolone, in 12 healthy volunteers (9 men and 3 women). The subjects were infused with a standard therapeutic dose of Fleroxacin (400 mg) supplemented with approximately 20 mCi of [18F]Fleroxacin. Serial PET images were made and blood samples were collected for 8 h, starting at the initiation of the infusion. The subjects were then treated with unlabeled drug for 3 days (400 mg/day). On the fifth day, infusion of radiolabeled drug, PET imaging, and blood collection were repeated. In most organs, there was rapid accumulation of radiolabeled drug, with stable levels achieved within 1 h after completion of the infusion. Especially high peak concentrations (in micrograms per gram) were achieved in the kidney (> 34), liver (> 25), lung (> 20), myocardium (> 19), and spleen (> 18). Peak concentrations of drug more than two times the MIC for 90% of Enterobacteriaceae strains tested (> 10-fold for most organisms) were achieved in all tissues except the brain and remained above this level for more than 6 to 8 h. The plateau concentrations in tissues (2 to 8 h, in micrograms per gram +/- standard error of the mean) of drug were as follows: brain, 0.83 +/- 0.032; myocardium, 4.53 +/- 0.24; lung, 5.80 +/- 0.48; liver, 7.31 +/- 0.33; spleen, 6.00 +/- 0.47; bowel, 3.53 +/- 0.74; kidney, 8.85 +/- 0.64; bone, 2.87 +/- 0.29; muscle, 4.60 +/- 0.33; prostate, 4.65 +/- 0.48; uterus, 3.87 +/- 0.39; breast, 2.68 +/- 0.11; and blood, 2.35 +/- 0.09. Concentrations of Fleroxacin in tissue were similar in males and females, before and after pretreatment with unlabeled drug.

  • pharmacokinetics of 18f labeled Fleroxacin in rabbits with escherichia coli infections studied with positron emission tomography
    Antimicrobial Agents and Chemotherapy, 1992
    Co-Authors: Alan J Fischman, Barbara Prosser, Roy Cleeland, Eli Livni, John W Babich, Nathaniel M Alpert, Yuying Liu, E Thom, Ronald J Callahan, J A Correia
    Abstract:

    18F-labeled Fleroxacin was used to measure the pharmacokinetics of Fleroxacin in healthy and infected animals by positron emission tomography (PET) and tissue radioactivity measurements. In all experiments, a pharmacological dose of unlabeled drug (10 mg/kg) was coinjected with the tracer. The pharmacokinetics of [18F]Fleroxacin was measured in groups of healthy mice (n = six per group) at 10, 30, 60, and 120 min after injection and in groups of rats with Escherichia coli thigh infections (n = six per group) at 60 and 120 min after injection by radioactivity measurements in excised tissues. In healthy rabbits (n = 4) and in rabbits with E. coli thigh infections (n = 4), tissue concentrations of drug were determined by serial PET imaging over 2 h; after the final image was acquired, animals were sacrificed and concentrations measured by PET were compared with the results of tissue radioactivity measurements. In all three species, there was rapid equilibration of [18F]Fleroxacin to significant concentrations in most peripheral organs; low concentrations of drug were detected in the brain. Accumulations of radiolabeled drug in infected and healthy thigh muscles were similar. Peak concentrations of drug of more than three times the MIC for 90% of members of the family Enterobacteriaceae (greater than 100-fold for most organisms) were achieved in all tissues except brain and remained above this level for more than 2 h. Especially high peak concentrations were achieved in the kidney (greater than 75 micrograms/g), liver (greater than 50 micrograms/g), blood (greater than 25 micrograms/g), and bone and lung (greater than 10 micrograms/g). Since the MICs for 90% of all Enterobacteriaceae are <2 micrograms/ml, Fleroxacin should be particularly useful in treating gram-negative infections affecting these tissues. In contrast, the low concentration of drug delivered to the brain should limit the toxicity of the drug for the central nervous system.

Nathaniel M Alpert - One of the best experts on this subject based on the ideXlab platform.

  • pharmacokinetics of 18f Fleroxacin in patients with acute exacerbations of chronic bronchitis and complicated urinary tract infection studied by positron emission tomography
    Antimicrobial Agents and Chemotherapy, 1996
    Co-Authors: Alan J Fischman, Eli Livni, John W Babich, Nathaniel M Alpert, Ali A Bonab, S Chodosh, Francis J Mcgovern, P Kamitsuka, Yuying Liu, Roy Cleeland
    Abstract:

    The pharmacokinetics of Fleroxacin, a new broad-spectrum fluoroquinolone, were measured by positron emission tomography (PET) with [18F]Fleroxacin in five patients with acute bacterial exacerbations of chronic bronchitis and in five patients with symptomatic, complicated urinary tract infection. Two studies were performed with each patient, one within 24 h of the initiation and one within 24 h of the completion of a 7-day course of Fleroxacin, 400 mg/day. For each study, the patient received an infusion of that day's therapeutic dose of Fleroxacin (400 mg) supplemented with approximately 740 MBq of [18F]Fleroxacin, and serial PET images and blood samples were collected for 6 to 8 h starting at the initiation of the infusion. Between studies, the drug was administered orally. In all infected tissues, there was rapid accumulation of radiolabeled drug, with stable levels achieved within 1 h after completion of the infusion. In kidneys, accumulation was greater in the presence of active infection (P 30 micrograms/g), prostate glands (> 11 micrograms/g), and lungs (> 14 micrograms/g). Plateau concentrations (2 to 8 h; given as mean micrograms per gram +/- standard error of the mean) of drug in kidneys (15.11 +/- 0.55), prostate glands (5.08 +/- 0.19), and lungs (5.75 +/- 0.22) were also well above the MIC90 for most relevant pathogens. All patients had a good therapeutic response to Fleroxacin.

  • tissue pharmacokinetics of Fleroxacin in humans as determined by positron emission tomography
    International Journal of Antimicrobial Agents, 1994
    Co-Authors: Barbara Prosser, Roy Cleeland, Eli Livni, John W Babich, Nathaniel M Alpert, Yuying Liu, E Thom, Robert H Rubin, Alan J Fischman
    Abstract:

    Abstract The delivery of Fleroxacin, a new broad-spectrum fluoroquinolone, to the major organs of the body was studied in 12 normal human volunteers (nine men and three women), utilizing positron emission tomography (PET). Following the infusion of 20 mCi of [ 18 F]Fleroxacin in conjuction with a standard therapeutic dose of 400 mg, images were acquired over 8 h. Beginning the next day, the subjects received unlabeled drug at a dose of 400 mg/day for 3 days, with a repeat PET study on the fifth day. Fleroxacin is distributed widely throughout the body, with the notable exception of the central nervous system, with stable levels achieved within 1 h after completion of the infusion. Especially high peak concentrations (⩾18 μ g/g) were achieved in the kidney, liver, lung myocardium, and spleen. The mean plateau concentrations (2–8 h post-infusion, μg/g) were: brain 0.83; myocardium, 4.53; lung, 5.80, liver, 7.31; spleen, 6.00; bowel, 3.53; kidney, 8.85; bone, 2.87; muscle, 4.60; prostate, 4.65; uterus, 3.87; breast, 2.68; and blood, 2.35. Repetitive dosing had no significant effect on the pharmacokinetics of the drug. Since the MIC 90 's of the family Enterobacterioaceae and Neisseria gonorrhoeae are μ g/ml, with the great majority of the individual species ⩾1 μ g/ml, these results suggest that a single daily dose of 400 mg of Fleroxacin should be effective in the treatment of infections such as urinary tract infection and gonorrhea.

  • pharmacokinetics of 18f Fleroxacin in healthy human subjects studied by using positron emission tomography
    Antimicrobial Agents and Chemotherapy, 1993
    Co-Authors: Alan J Fischman, Barbara Prosser, Roy Cleeland, Eli Livni, John W Babich, Nathaniel M Alpert, Yuying Liu, E Thom, J A Correia, H W Strauss
    Abstract:

    Positron emission tomography (PET) with [18F]Fleroxacin was used to study the pharmacokinetics of Fleroxacin, a new broad-spectrum fluoroquinolone, in 12 healthy volunteers (9 men and 3 women). The subjects were infused with a standard therapeutic dose of Fleroxacin (400 mg) supplemented with approximately 20 mCi of [18F]Fleroxacin. Serial PET images were made and blood samples were collected for 8 h, starting at the initiation of the infusion. The subjects were then treated with unlabeled drug for 3 days (400 mg/day). On the fifth day, infusion of radiolabeled drug, PET imaging, and blood collection were repeated. In most organs, there was rapid accumulation of radiolabeled drug, with stable levels achieved within 1 h after completion of the infusion. Especially high peak concentrations (in micrograms per gram) were achieved in the kidney (> 34), liver (> 25), lung (> 20), myocardium (> 19), and spleen (> 18). Peak concentrations of drug more than two times the MIC for 90% of Enterobacteriaceae strains tested (> 10-fold for most organisms) were achieved in all tissues except the brain and remained above this level for more than 6 to 8 h. The plateau concentrations in tissues (2 to 8 h, in micrograms per gram +/- standard error of the mean) of drug were as follows: brain, 0.83 +/- 0.032; myocardium, 4.53 +/- 0.24; lung, 5.80 +/- 0.48; liver, 7.31 +/- 0.33; spleen, 6.00 +/- 0.47; bowel, 3.53 +/- 0.74; kidney, 8.85 +/- 0.64; bone, 2.87 +/- 0.29; muscle, 4.60 +/- 0.33; prostate, 4.65 +/- 0.48; uterus, 3.87 +/- 0.39; breast, 2.68 +/- 0.11; and blood, 2.35 +/- 0.09. Concentrations of Fleroxacin in tissue were similar in males and females, before and after pretreatment with unlabeled drug.

  • pharmacokinetics of 18f labeled Fleroxacin in rabbits with escherichia coli infections studied with positron emission tomography
    Antimicrobial Agents and Chemotherapy, 1992
    Co-Authors: Alan J Fischman, Barbara Prosser, Roy Cleeland, Eli Livni, John W Babich, Nathaniel M Alpert, Yuying Liu, E Thom, Ronald J Callahan, J A Correia
    Abstract:

    18F-labeled Fleroxacin was used to measure the pharmacokinetics of Fleroxacin in healthy and infected animals by positron emission tomography (PET) and tissue radioactivity measurements. In all experiments, a pharmacological dose of unlabeled drug (10 mg/kg) was coinjected with the tracer. The pharmacokinetics of [18F]Fleroxacin was measured in groups of healthy mice (n = six per group) at 10, 30, 60, and 120 min after injection and in groups of rats with Escherichia coli thigh infections (n = six per group) at 60 and 120 min after injection by radioactivity measurements in excised tissues. In healthy rabbits (n = 4) and in rabbits with E. coli thigh infections (n = 4), tissue concentrations of drug were determined by serial PET imaging over 2 h; after the final image was acquired, animals were sacrificed and concentrations measured by PET were compared with the results of tissue radioactivity measurements. In all three species, there was rapid equilibration of [18F]Fleroxacin to significant concentrations in most peripheral organs; low concentrations of drug were detected in the brain. Accumulations of radiolabeled drug in infected and healthy thigh muscles were similar. Peak concentrations of drug of more than three times the MIC for 90% of members of the family Enterobacteriaceae (greater than 100-fold for most organisms) were achieved in all tissues except brain and remained above this level for more than 2 h. Especially high peak concentrations were achieved in the kidney (greater than 75 micrograms/g), liver (greater than 50 micrograms/g), blood (greater than 25 micrograms/g), and bone and lung (greater than 10 micrograms/g). Since the MICs for 90% of all Enterobacteriaceae are <2 micrograms/ml, Fleroxacin should be particularly useful in treating gram-negative infections affecting these tissues. In contrast, the low concentration of drug delivered to the brain should limit the toxicity of the drug for the central nervous system.