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Interaction between isoniazid and theophylline.

P Höglund, L G Nilsson, O Paulsen

European Journal of Respiratory Diseases

|February 1, 1987

Summary

Drug interactions involving theophylline are clinically significant due to its narrow therapeutic range. This study found that oral isoniazid significantly increases theophylline plasma levels and decreases its clearance, contrary to expectations.

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Area of Science:

Pharmacology
Drug Metabolism
Clinical Pharmacy

Background:

Theophylline, a drug with a narrow therapeutic index, is known to interact with other medications.
Interactions are typically expected with drugs metabolized by oxidative enzymes.
Previous reports suggested increased theophylline clearance with oral isoniazid, contrary to expectations.

Purpose of the Study:

To investigate the metabolic interaction between theophylline and isoniazid.
To determine the effect of oral isoniazid on the pharmacokinetics of intravenous theophylline.

Main Methods:

Intravenous theophylline infusions were administered to subjects.
Theophylline pharmacokinetics were assessed with and without concomitant oral isoniazid administration.
Theophylline plasma levels and clearance were measured.

Main Results:

Oral isoniazid significantly increased plasma levels of intravenously infused theophylline.
A corresponding significant decrease in the plasma clearance of theophylline was observed with oral isoniazid.
The observed interaction was independent of the subjects' acetylator status.
A non-statistically significant increase in isoniazid half-life and AUC was noted in the presence of theophylline.

Conclusions:

Oral isoniazid significantly alters the pharmacokinetics of theophylline, increasing its plasma levels and decreasing its clearance.
This interaction is clinically relevant for patients receiving both theophylline and isoniazid.
The findings challenge the assumption that interactions are limited to drugs metabolized by oxidative enzymes.

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