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Pharmacology: Pharmacokinetics: Absorption: After oral administration, the bioavailability of azithromycin is approximately 37%. Peak plasma levels are reached after 2-3 hours (Cmax after a single dose of 500 mg orally was approximately 0.4 mg/L).
Distribution: Kinetic studies have shown markedly higher azithromycin levels in tissue than in plasma (up to 50 times the maximum observed concentration in plasma) indicating that the active substance is heavily tissue bound (steady state distribution volume of approximately 31 L/kg). Concentrations in target tissues such as lung, tonsil, and prostate exceed the MIC90 for likely pathogens after a single dose of 500 mg. In experimental in vitro and in vivo studies azithromycin accumulates in the phagocytes, freeing is stimulated by active phagocytosis. In animal studies, this process appeared to contribute to the accumulation of azithromycin in the tissue. In serum, the protein binding of azithromycin is variable and depending on the serum concentration varies from 50% in 0.05 mg/L to 12% in 0.5 mg/L.
Excretion: Plasma terminal elimination half-life closely reflects the tissue depletion half-life of 2 to 4 days. About 12% of an intravenously administered dose is excreted in the urine unchanged over a period of 3 days; the majority in the first 24 hours. Biliary excretion of azithromycin, predominantly in unchanged form, is a major route of elimination. The identified metabolites (formed by N- and O-demethylising, by hydroxylising of the desosamine and aglycone rings, and by the splitting of the cladinose conjugate) are microbiologically inactive. After a 5 day treatment, slightly higher (29%) AUC values were seen in the elderly volunteers (> 65 years of age) compared to the younger volunteers (< 45 years of age). However, these differences are not regarded as clinically relevant; therefore, a dose adjustment is not recommended.
