Drug Interaction Study of Azithromycin and Theophylline

A Pharmacokinetic Drug Interaction Study to Evaluate the Effect of Azithromycin on the Steady-State Plasma Levels of Theophylline in a Chinese Population

Macrolides are potent inhibitors of cytochrome P450 isoenzyme 3A4（CYP3A4）and thus interfere with the pharmacokinetics of many other drugs that are metabolised by this enzyme like theophylline.The aim of this study is to determine whether azithromycin can effect theophylline metabolism in patients.

In this non-blinded,auto-control study,patients with Chronic Obstructive Pulmonary Disease（COPD）or asthma will serve as their own controls during the 2-week treatment phase.The subjects will be co-administered oral doses of sustained release theophylline (100mg tablets,twice daily) and azithromycin (2x250mg capsules,once daily )in the first week.Then patients will received theophylline therapy alone with the same dose in the second week.Blood samples for the measurement of theophylline plasma concentrations will be collected on Days 8 and 15 prior to dosing.All adverse events whether elicited by query, spontaneously reported or observed by clinic staff will be evaluated by the investigator and reported in the subject's case report form.

Inclusion Criteria:

• patients with COPD or asthma，aged 18-75 years;
• regularly visiting our hospital;
• meeting the indications for azithromycin and theophylline simultaneously;

Exclusion Criteria:

• patients with renal or hepatic dysfunction;
• patients with congestive heart failure;
• patients with hypothyroidism or hyperthyroidism;
• patients taking drugs likely to affect the theophylline metabolism in the preceding week;
• patients with severe chronic obstructive pulmonary disease,asthma or respiratory infection;