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Inhibition of Theophylline Elimination by Diltiazem Therapy

To investigate the effects of diltiazem on theophylline pharmacokinetics, nine healthy male subjects (four smokers and five nonsmokers) received intravenous aminophylline (6 mg/kg) prior to and following 10 days of oral diltiazem therapy. Theophylline half‐life increased significantly whereas total body clearance showed a significant decrease following diltiazem. Volume of distribution was unchanged. The small group of smokers had a significantly greater increase in theophylline half‐life than the nonsmokers. Inhibition of metabolism of theophylline by diltiazem likely explains the significant changes in theophylline pharmacokinetics. A clinically important drug interaction may occur with theophylline when diltiazem therapy is given concurrently.