Diltiazem Treatment Impairs Theophylline Elimination in Patients with Bronchospastic Airway Disease

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Abstract

Summary

On the basis of reports that diltiazem may bind to the hepatic mi-crosomal enzymes and inhibits the metabolism of some co-administered drugs, and to determine the effects of diltiazem on theophylline pharmacokinetics in patients with bronchospastic airway disease, we have investigated the effect of a 180-mg daily dose of oral diltiazem during 5 days on theophylline clearance in eight patients with that disease. Theophylline half-life increased 24%, from 5.7 ± 1 to 7.5 ± 1.8 h (p < 0.05), and total body theophylline clearance showed a decrease of 22%, from 87.3 ± 20 to 68.3 ± 18.6 ml/min (p < 0.05) after diltiazem therapy. The apparent volume of distribution was unchanged. This reduction in theophylline clearance is likely produced by inhibition of its metabolism by diltiazem. A clinically important drug interaction may occur with theophylline when diltiazem therapy is given concurrently in patients with bronchospastic airway disease.

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