Tuberc Respir Dis.  1998 Jun;45(3):546-552. 10.4046/trd.1998.45.3.546.

Effects of Erythromycin and New Macrolides on the Serum Theophylline Level and Clearance

Affiliations
  • 1Department of Internal Medicine, Chukbuk National University Medical School, Chonju, Korea.

Abstract

BACKGROUND: Up to 90% of a theophylline dose is biotransformed, by interaction with one or more the variants of the cytochrome P-450 drug metabolism system. Macrolides affect the elimination of theophylline by influencing on the microsomal enzyme systems. We evaluate the effect of erythromycin and new macrolides on the serum theophylline level and clearance. METHOD: Subjects consisted of moderate asthmatic patients with normal renal and hepatic functions. All subjects were non-smokers and treated with oral theophylline 400mg per day. We randomly assigned 53 patients into four groups. Each group was treated with one macrolides, the first group erythromycin(n: 19, 500 mg bid), second roxitbromycin (n: 14. 150 mg bid), third clarithromycin (n: 10, 250 mg bid) and fourth azithromycin(n: 10, 250 mg bid). We measured the serum theophylline level and clearance at three intervals, at pretreatment, after the first and fourth week after receiving the following macrolides, erythromycin, roxithromycin and clarithromycin. When azithromycin was administered, the serum theophylline level was measured at pretreatment and after one week of treatment They were measured by a computerized program of Bayesian method.
RESULTS
When compared with control, erytbromycin and roxithromycin-treated groups had a significantly elevated serum theophylline level and decreased clearance. However, there were no significant changes of the serum theophylline level and clearance in clarithromycin and azithromycin-treated groups.
CONCLUSION
These results suggest that theophylline dose may need to be readjusted and have periodic drug monitoring when erythromycin or roxithromycin is administered concurrenfly.

Keyword

Theophylline concentration; Theophylline clearnace; Erythromycin; New Macrolides

MeSH Terms

Azithromycin
Bayes Theorem
Clarithromycin
Cytochrome P-450 Enzyme System
Drug Monitoring
Erythromycin*
Humans
Macrolides*
Metabolism
Roxithromycin
Theophylline*
Azithromycin
Clarithromycin
Cytochrome P-450 Enzyme System
Erythromycin
Macrolides
Roxithromycin
Theophylline
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