Pharmacokinetic drug interactions with theophylline

Area of Science:

• Pharmacology
• Drug Metabolism

Background:

• Theophylline is extensively metabolized in the liver, primarily via microsomal enzyme systems.
• Concurrent administration of other drugs can alter theophylline elimination through various mechanisms, including enzyme induction/inhibition and altered hepatic uptake.

Purpose of the Study:

• To review the impact of commonly coadministered drugs on theophylline pharmacokinetics.
• To provide guidance on potential theophylline dosage adjustments based on interacting medications.

Main Methods:

• Literature review of studies investigating drug interactions with theophylline.
• Analysis of reported changes in theophylline clearance and dosage recommendations.

Main Results:

• Several drugs, including phenobarbitone, phenytoin, carbamazepine, rifampicin, isoniazid, and sulphinpyrazone, increase theophylline clearance, requiring dose increases of 20-50%.
• Other drugs, such as erythromycin, propranolol, isoprenaline, cimetidine, oral contraceptives, triacetyloleandomycin, and high-dose allopurinol, decrease theophylline clearance, necessitating dose reductions of 20-50%.
• Many drugs, including ranitidine, certain antibiotics, beta-blockers, and antacids, do not significantly affect theophylline pharmacokinetics, offering safer coadministration options.

Conclusions:

• Drug interactions significantly impact theophylline elimination, often requiring careful dosage adjustments guided by plasma theophylline levels.
• Understanding these interactions is critical for optimizing theophylline therapy and minimizing adverse events.
• Identifying interacting drugs that do not affect theophylline clearance provides valuable clinical alternatives.