DILTIAZEM TREATMENT IMPAIRS THEOPHYLLINE ELIMINATION IN PATIENTS WITHBRONCHOSPASTIC AIRWAY DISEASE

On the basis of reports that diltiazem may bind to the hepatic microso mal enzymes and inhibits the metabolism of some co-administered drugs, and to determine the effects of diltiazem on theophylline pharmacokin etics in patients with bronchospastic airway disease, we have investig ated the effect of a 180-mg daily dose of oral diltiazem during 5 days on theophylline clearance in eight patients with that disease. Theoph ylline 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 th erapy. The apparent volume of distribution was unchanged. This reducti on in theophylline clearance is likely produced by inhibition of its m etabolism by diltiazem. A clinically important drug interaction may oc cur with theophylline when diltiazem therapy is given concurrently in patients with bronchospastic airway disease.