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Ceftriaxone diffusion into cardiac fibrin vegetation. Qualitative and quantitative evaluation by autoradiography
Author(s) -
Crémieux AC,
Mazière B.,
Vallois JM,
Ottaviani M.,
Bouvet A.,
Pocidalo JJ,
Carbon C.
Publication year - 1991
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1991.tb00701.x
Subject(s) - ceftriaxone , antibiotics , fibrin , endocarditis , in vivo , vegetation (pathology) , diffusion , pharmacokinetics , medicine , chemistry , microbiology and biotechnology , pharmacology , pathology , biology , immunology , physics , thermodynamics
Summary— Heterogeneous diffusion of some antibiotics into fibrin rich infectious processes is one explanation of the difficulty to cure infections such as endocarditis. Ceftriaxone is a β lactam antibiotic, potentially useful due to a broad spectrum of activity and its long elimination half‐life. We investigated by means of autoradiography the diffusion of labelled ceftriaxone into large infected cardiac vegetations obtained in a rabbit model of endocarditis. Ten d after infection 250 μCi 14 C ceftriaxone was injected over 30 min. Thirty min after the end of infusion (T30) vegetation/blood radioactivity ratio was 0.58 ± 0.4 ( n = 3). At T200, radioactivity decreased approximatively 3‐fold, in blood and in vegetations simultaneously. Autoradiography showed that at T30, ceftriaxone was 20–30 times more concentrated at the periphery of vegetation than in the core. Autoradiography obtained at T200 showed a progressive diffusion toward the core. The diffusion gradient may explain the fact that high local concentrations are necessary to sterilize vegetations. The pattern of diffusion of antibiotics in fibrin is an important pharmacokinetic parameter for predicting in vivo activity.