Pharmacokinetics of [18F]fleroxacin in healthy human subjects studied by using positron emission tomography

A. J. Fischman, E. Livni, J. Babich, N. M. Alpert, Y. Y. Liu, E. Thom, R. Cleeland, B. L. Prosser, J. A. Correia, H. W. Strauss, R. H. Rubin

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47 Scopus citations

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 ~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.

Original languageEnglish
Pages (from-to)2144-2152
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume37
Issue number10
DOIs
StatePublished - 1993
Externally publishedYes

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