All three macrolides have good oral bioavailability and diffuse into most tissues. However, they do not have as good CSF penetration as the beta-lactam antibiotics. Erythromycin has a short plasma half-life of around 90 minutes; hence it is generally dosed four times daily. Clarithromycin and azithromycin both have much longer half-lives. Azithromycin is converted in the liver to an active metabolite, and persists in tissues at high concentrations; thus it has the advantage of being able to be given as a single dose for some infections, allowing for directly observed therapy and assurance that the patient has taken the appropriate treatment. Azithromycin capsules need to be taken on an empty stomach, and should be dosed separately from iron or indigestion remedies. Azithromycin tablets are also available; these are 500mg (as opposed to 250mg) capsules, and do not have any food restrictions. All three macrolides are excreted in the bile.

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