Lack of effect of dirithromycin on theophylline pharmacokinetics in healthy volunteers

• Published in: Journal of antimicrobial chemotherapy Vol. 43; no. 5; pp. 733 - 736
• Main Author: McConnell, S. A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.05.1999; Oxford Publishing Limited (England)
• Subjects: Adult; Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Area Under Curve; Biological and medical sciences; Drug Interactions; Drug Therapy, Combination; Dyspepsia - chemically induced; Erythromycin - analogs & derivatives; Erythromycin - pharmacology; Female; Headache - chemically induced; Humans; Macrolides; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Respiratory system; Theophylline - adverse effects; Theophylline - pharmacokinetics; Tremor - chemically induced; Human; Drug combination; Toxicity; Bronchodilator; Oral administration; Dirithromycin; Bioavailability; Antiasthma agent; Normal; Macrolide; Antibiotic; Randomization; Clinical trial; Drug interaction; Xanthine derivatives; Antibacterial agent; Pharmacokinetics; Theophylline
• ISSN: 1460-2091; 0305-7453; 1460-2091
• DOI: 10.1093/jac/43.5.733

Twelve healthy volunteers were enrolled in an open-label, randomized, crossover study. Subjects received single doses of theophylline (5 mg/kg) alone and after a 10 day course of dirithromycin (two 250 mg tablets od). The study phases were separated by a 3 week washout period. Serum samples were collected before and for 24 h after theophylline doses. Serum theophylline concentrations were measured via a validated immunoassay system and the data were modelled via non-compartmental analysis. When the control phase (i.e. no dirithromycin) was compared with the treatment phase (i.e. with dirithromycin), theophylline exposures as measured by AUC0-->infinity were not significantly different: 141.7+/-25.9 and 136.4+/-33.1 mg x h/L respectively (P = 0.16). No significant changes in other theophylline pharmacokinetic parameters were evident. These results indicate that theophylline can be safely co-administered with dirithromycin.