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Increased Toxicity and Reduced Clearance of Lidocaine by Cimetidine

[+] Article, Author, and Disclosure Information

Grant support: grants GM 15431, AG 01395, and 5 MO1 RR95, U.S. Public Health Service, and a grant in aid from Smith Kline & French, Inc.

Dr. Feely was a Merck International Fellow in Clinical Pharmacology and the National University of Ireland Travelling Student in Pharmacology. Dr. Wood is the recipient of a Faculty Development Award from the Pharmaceutical Manufacturer's Association Foundation.

▸Requests for reprints should be addressed to Alastair J.J. Wood, M.B. Ch.B., Vanderbilt University Medical Center; Nashville, TN 37232.

Nashville, Tennessee

© 1982 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1982;96(5):592-594. doi:10.7326/0003-4819-96-5-592
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Cimetidine reduces liver blood flow and the systemic clearance of drugs, such as propranolol, that are highly extracted by the liver. In a randomized placebo-controlled study, we examined the influence of cimetidine, 300 mg four times daily for 1 d, on the disposition of lidocaine, 1 mg/kg body weight by a 10-minute intravenous infusion. Cimetidine reduced the systemic clearance of lidocaine from 766 ± 50 mL/min to 576 ± 47 mL/min (p < 0.05); the apparent volume of distribution at steady-state and the degree of plasma protein binding of lidocaine also were decreased. Five of the six subjects noted lidocaine toxicity during the cimetidine infusion in contrast to one subject on the placebo day. The peak lidocaine concentration (mean ± SE) was 50% ± 10% higher when subjects received cimetidine. This study provides additional evidence that the effect of cimetidine on the elimination of other drugs has multiple factors, and shows a previously unrecognized mechanism, involving altered initial drug distribution, whereby the interaction of cimetidine with other drugs may cause toxicity.





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