TY - JOUR
T1 - Pharmacokinetics of [18F]fleroxacin in healthy human subjects studied by using positron emission tomography
AU - Fischman, A. J.
AU - Livni, E.
AU - Babich, J.
AU - Alpert, N. M.
AU - Liu, Y. Y.
AU - Thom, E.
AU - Cleeland, R.
AU - Prosser, B. L.
AU - Correia, J. A.
AU - Strauss, H. W.
AU - Rubin, R. H.
PY - 1993
Y1 - 1993
N2 - 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 ~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.
AB - 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 ~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.
UR - http://www.scopus.com/inward/record.url?scp=0027330326&partnerID=8YFLogxK
U2 - 10.1128/AAC.37.10.2144
DO - 10.1128/AAC.37.10.2144
M3 - Article
C2 - 8257137
AN - SCOPUS:0027330326
SN - 0066-4804
VL - 37
SP - 2144
EP - 2152
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 10
ER -