Diltiazem treatment impairs theophylline elimination in patients with bronchospastic airway disease

On the basis of reports that diltiazem may bind to the hepatic microsomal 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.