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Inhibition of Theophylline Clearance by Cimetidine but not Ranitidine
J. Robert Powell, PharmD;
John F. Rogers, MD;
William A. Wargin, PhD;
Robert E. Cross, PhD;
Fred N. Eshelman, PharmD
Arch Intern Med. 1984;144(3):484-486.
Abstract
• This study was designed to compare the effects of equivalent therapeutic doses of two H2 antagonists, cimetidine and ranitidine, on theophylline pharmacokinetics and to determine whether the previously described cimetidine-theophylline interaction is dose dependent. Twelve healthy adult men were given a 6-mg/kg intravenous aminophylline dose on four occasions. Subjects were randomly assigned four treatments: no treatment (control); cimetidine, 1,200 mg/day; cimetidine, 2,400 mg/day; and ranitidine, 300 mg/day. Cimetidine, 1,200 mg/day, significantly decreased theophylline clearance by 36% (range, 22% to 49%) and increased the mean elimination half-life from 5.7 hours (control) to 9.2 hours. A significant difference was not found beween the two cimetidine dosages, indicating dose independence of the interaction over the dosage range studied. Ranitidine did not significantly alter theophylline pharmacokinetics. Theophylline plasma protein binding was not affected by any treatment. The relative effects of cimetidine and ranitidine on the elimination of cytochrome P-450 metabolized drugs such as theophylline indicate a useful property of ranitidine as compared with cimetidine.
(Arch Intern Med 1984;144:484-486)
Author Affiliations
From the Divisions of Pharmacy Practice and Pharmaceutics, School of Pharmacy (Drs Powell, Wargin, and Eshelman), and the Division of Clinical Pharmacology (Drs Powell and Rogers) and the Department of Laboratory Medicine (Drs Powell, Rogers, and Cross), School of Medicine, University of North Carolina, Chapel Hill; and Glaxo, Inc, Research Triangle Park, NC (Dr Eshelman).
Footnotes
Accepted for publication Oct 10, 1983.
Reprint requests to Division of Clinical Pharmacology, 104 MacNider Bldg 202H, University of North Carolina, Chapel Hill, NC 27514 (Dr Powell).
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