The pharmacokinetic and microbiological data of roxithromycin, an oral semisynthetic macrolide, and its clinical use in respiratory infections in Japanese patients are reviewed. In healthy men the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of roxithromycin increase with increasing dosage, as does urinary drug excretion. The drug's Cmax and half-life are increased compared with erythromycin, josamycin and miocamycin. Maximum sputum and plasma drug concentrations were higher in patients with chronic bronchitis receiving roxithromycin 150mg than in those receiving erythromycin 400mg. Uptake of roxithromycin into polymorphonuclear cells was proportionally greater than that of erythromycin and josamycin. Roxithromycin showed good in vitro activity against respiratory pathogens, including intracellular pathogens such as Legionella pneumophila and Mycoplasma pneumoniae, although it had only about one-quarter of the activity of erythromycin against Staphylococcus aureus and Streptococcus pneumoniae. High success rates were obtained in patients with acute pneumonia (79%) and chronic obstructive airways disease (75%) receiving roxithromycin in a noncomparative trial in 378 patients with respiratory tract infection, and roxithromycin and miocamycin showed similar efficacy in a double-blind study.Thus, roxithromycin concentrations achieved in sputum, plasma and intracellularly provide effective antimicrobial activity against respiratory pathogens, and this has been confirmed by the results of clinical trials.Roxithromycin (erythromycin-9-0-2-methoxyethoxy-methyl oxime) is a new oral semisynthetic macrolide. Its antimicrobial activity against respiratory intracellular pathogens such as Legionella (Hara et al. 1987) and Chlamydia spp. (Bowie et al. 1987) is more potent than that of erythromycin. The pharmacokinetic properties of roxithromycin include high stability in gastric acid, good absorption from the gastrointestinal tract achieving high plasma concentrations, and good tissue distribution (Puri & Lassman 1987). This paper reviews the pharmacokinetic, microbiological and clinical data on roxithromycin in respiratory infections in Japan.
Pharmacokinetic StudiesSeveral studies designed to determine the pharmacokinetics of roxithromycin in normal and special populations have been conducted in Japan. 24 healthy young men received a single 150, 300 or 600mg dose of roxithromycin, and blood samples