Roxithromycin: a pharmacokinetic review of a macrolide

In humans, roxithromycin is rapidly absorbed from the gastrointestinal tract producing peak levels (Cmax) within 2 h. The drug is eliminated with a half-life (T1/2) of about 10 h. Roxithromycin is not extensively metabolized. Approximately 53% is excreted in the faeces and about 10% of the dose is eliminated in urine. Although dose-dependency (with doses from 150 to 450 mg) was observed for certain pharmacokinetic parameters, dose-proportionality could only be demonstrated with urine data. During multiple dosing, steady state is usually reached by day four and is dose-dependent. There is a slight but clinically unimportant increase in the T1/2 of the drug with repeated administration. While the rate of absorption is not affected by age, the rate of elimination and renal clearance are decreased in the elderly subjects. No significant differences were observed for Cmax and Tmax between normal and renally impaired subjects. AUCs and elimination T1/2 were greater, and significantly less drug was excreted in renally impaired patients. In patients with liver cirrhosis Cmax, Tmax, and AUCs are not affected. The bioavailability of the drug is not affected to a clinically important extent when it is given either with milk or food. Less than 0.05% of a single 300 mg dose is excreted in the breast milk of lactating women. After oral dosing a very high concentration of roxithromycin is achieved in pulmonary, prostatic, and tonsillar tissues. However, roxithromycin was not detected in the cerebrospinal fluid of subjects with non-inflamed meninges. It is concluded that 150 mg roxithromycin twice daily or 300 mg once a day should provide plasma levels above the minimum inhibitory concentrations required for antibacterial activity.