[Azithromycin: tissue pharmacology].

Abstract

Among macrolide derivatives, azithromycin which is an azalide, is a totally original new drug as to its pharmacokinetics in serum and tissues. Compared to reference compounds such as erythromycin or roxithromycin, pharmacokinetic parameters of azithromycin are characterized by: (i) much lower serum concentrations; (ii) a much longer elimination half-life (48-96 h); (iii) high and persistent tissue concentrations. The latter characteristic has been demonstrated in animal models (experimental H. influenzae pneumonia in mice) and in human studies. In lung parenchyma, azithromycin concentrations were higher and more persistent (72 h) in infected mice (12 mg/kg) as compared to non infected mice (controls) receiving the same dose of azithromycin (50 mg/kg); this may result from high intracellular concentrations in polymorphonuclear leucocytes and release of the drug at pulmonary sites of infection. In man, concentrations of azithromycin have been measured in lung parenchyma, bronchial secretions, tonsils, during exploratory or surgical conditions. After a single dose of 500 mg of azithromycin, local levels may reach up to 10 mg/kg with persistence of high levels for > or = 72 h in lungs, tonsils, sinus and bronchial secretions (1.5 to 8.6 mg/kg or mg/l). Five consecutive doses of azithromycin (500 mg per day) maintained for 10 days tonsil concentrations higher than the MICs for susceptible bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)