Reduced serum theophylline concentrations after discontinuation of azithromycin: evidence for an unusual interaction

A 68-year-old man receiving long-term therapy with oral sustained-release theophylline 450 mg twice/day was admitted to the hospital after failing treatment with azithromycin for an acute exacerbation of obstructive lung disease. Peak serum theophylline concentration was 20 microg/ml (normal 10-20 microg/ml). Azithromycin was discontinued and the theophylline dosage reduced by 33%. The subsequent 80% decrease in serum theophylline to 4.6 microg/ml was unexpectedly large. Two rechallenges produced similar transient depressions of serum theophylline concentrations after withdrawal of azithromycin, suggesting an interaction. Withdrawal of azithromycin may leave an increased number of active enzyme sites available as the drug is cleared from the system. In some circumstances, it may be useful for pharmacokinetic interaction studies to continue measuring concentrations after the suspected interacting agent is stopped.