Drug Interaction Study of Azithromycin and Theophylline

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Chronic Obstructive Pulmonary Disease, Asthma

Intervention / Treatment
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* Drug: Theophylline with azithromycin
* Drug: Theophylline alone


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Theophylline with azithromycin<br>steady-state plasma concentration of theophylline in the presence of azithromycin | Drug: Theophylline with azithromycin<br>* Drug: Theophylline(100mg,sustained release tablets). Multi-dose of theophylline(100mg,twice daily) will administered at 8 am and 8 pm from day 1 to day 7. Drug:Azithromycin(250mg, capsules). Multi-dose of azithromycin(500mg,once daily) will administered at 8 pm from day 1 to day 7.<br>|
| Active Comparator: Theophylline alone<br>steady-state plasma concentration of theophylline alone | Drug: Theophylline alone<br>* Drug: Theophylline(100mg,sustained release tablet). Multi-dose of theophylline(100mg,twice daily) will administered at 8 am and 8 pm from day 8 to day 14.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| steady-state plasma concentration of theophylline | Theophylline and it's metabolite(1,3-dimethyluric) blood concentration | blood samples for theophylline will be collected on Days 8 and 15 before dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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azithromycin, theophylline, CYP3A4