[The particular case of azalides: antibiotic diapedesis. Experimental data from a murine model of pneumococcal pneumonia].
The relations between the clinical efficacy, phagocytic transport phenomena, tissular and sera kinetics have been assessed in a pneumonia murine model. At first, the correlation between the clinical efficacy and pharmacokinetics characteristics has been studied for the erythromycin, spiramycin, roxithromycin, clarithromycin and azithromycin. An in vivo clinical efficacy hierarchy has been established (azi > ery > roxi = azi > spira). A hierarchy identical to the clinical efficacy, has been recognised for the pulmonary elimination half lives and the pulmonar AUC. These could be considered as predictive of these antibiotics activity in the respiratory infections. In a second time, the tissular pharmacokinetics of the azithromycin in leukopenic mice allowed to confirm the leukocytes role in the transport and release of this antibiotic in the midst of the infections site. Finally, this antibiotic demonstrated its efficacy in a bacterienic infection even when administered at a low dosage thus allowing to have sera concentrations identical to those obtained in human clinical case and close to MIC's for S. pneumoniae. The pharmacokinetic novelty displayed by its strong tissular penetration can explain its remarkable efficacy.
INSERM, U13, Groupe Hospitalier Bichat, Claude-Bernard, Paris, France.
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Pocidalo
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D017963:Azithromycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017291:Clarithromycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004195:Disease Models, Animal; D004917:Erythromycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D051379:Mice; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000401:mortality; D015575:Roxithromycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015572:Spiramycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D015575:Roxithromycin; D004917:Erythromycin; D015572:Spiramycin; D017963:Azithromycin; D017291:Clarithromycin
Le cas particulier des azalides: l'antibiodiapédèse. Données expérimentales à partir d'un modèle murin de pneumonie à pneumocoque.