Effect of low-dose macrolide antibiotics on theophylline disposition in pediatric patients

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Low-dose macrolide antibiotics are administered for the treatment of certain chronic inflammatory sinopulmonary diseases (e.g., sinusitis and panbronchiolitis). Because 14-membered ring macrolide antibiotics administered at antimicrobial doses have been suggested to elicit a significant inhibitory effect on the hepatic metabolism of theophylline, we studied whether low-dose macrolide antibiotic therapy also evokes a clinically relevant alteration in the disposition of theophylline. The steady-state serum theophylline concentration and the urinary concentrations of theophylline and its metabolites [i.e., 1-methyluric acid (1MU), 3-methylxanthine (3MX), 1, 3-dimethyluric acid (DMU), and caffeine] were examined in nine stable asthmatic children who received both theophylline and lowdose erythromycin or clarithromycin (12.3±4.5mg/kg body weight/day) and in ten children who received theophylline alone.An immunoassay and high-performance liquid chromatography with ultraviolet detection (HPLC-UV) were used for serum and urinary drug assay, respectively. Results demonstrated no significant differences in serum theophylline concentration, the metabolic clearance of theophylline to its metabolites, and the renal clearance of theophylline between the two groups. In conclusion, the administration of low-dose macrolide antibiotics for the treatment of sinopulmonary diseases would not stipulate a dosage reduction of concomitantly administered theophylline in pediatric patients

Effect of low-dose macrolide antibiotics on theophylline disposition in pediatric patients

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