PARTICULAR CASE OF AZALIDES - ANTIBIOTIC DIAPEDESIS MEDIATE BY POLYNUCLEAR CELLS, EXPERIMENTAL-DATA FROM PNEUMOCOCCAL PNEUMONIA MURINE MODEL

The relations between the clinical efficacy, phagocytic transport phen omena, tissular and sera kinetics have been assessed in a pneumonia mu rine model. At first, the correlation between the clinical efficacy an d pharmacokinetics characteristics has been studied for the erythromyc in, spiramycin, roxithromycin, clarithromycin and azithromycin. An in vivo clinical efficacy hierarchy has been established (azi > ery > rox i = azi > spiral. A hierarchy identical to the clinical efficacy, has been recognised for the pulmonary elimination half lives and the pulmo nar 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 co nfirm the leukocytes role in the transport and release of this antibio tic in the midst of the infections site. Finally, this antibiotic demo nstrated its efficacy in a bacterienic infection even when administere d 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. pne umoniae. The pharmacokinetic novelty displayed by its strong tissular penetration can explain its remarkable efficacy.