LIDOCAINE METABOLITE 2,6-XYLIDINE FOUND IN HUMAN LIVER SLICES
This article was originally published in The Tan Sheet
Executive Summary
LIDOCAINE METABOLITE 2,6-XYLIDINE FOUND IN HUMAN LIVER SLICES, according to preliminary study results reported at a June 10 meeting of FDA's Anesthetic and Life Support Drugs Advisory Committee. "The important finding is that xylidine itself is produced by human liver slices," FDA Division of Clinical Pharmacology Branch Chief John Strong, PhD, asserted at the meeting. While researchers have "known for years" that lidocaine is broken down by the liver through a number of steps, Strong said, it was not known whether 2,6-xylidine was one of the intermediate compounds produced in that process.
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LIDOCAINE METABOLITE 2,6-XYLIDINE FOUND IN HUMAN LIVER SLICES, according to preliminary study results reported at a June 10 meeting of FDA's Anesthetic and Life Support Drugs Advisory Committee. "The important finding is that xylidine itself is produced by human liver slices," FDA Division of Clinical Pharmacology Branch Chief John Strong, PhD, asserted at the meeting. While researchers have "known for years" that lidocaine is broken down by the liver through a number of steps, Strong said, it was not known whether 2,6-xylidine was one of the intermediate compounds produced in that process. FDA agreed to conduct a study on human liver slices to determine whether 2,6-xylidine is metabolized by humans after data reviewed by the Anesthetic and Life Support Drugs Advisory Committee at an August 1993 meeting found the lidocaine metabolite to be carcinogenic to rats at high doses ("The Tan Sheet" Aug. 30, 1993, p. 10). The advisory committee tentatively concluded at the 1993 meeting that the rodent studies could not be linked to cancer in humans and allowed continued marketing of lidocaine for its present indications: OTC topical analgesia, Rx topical anesthesia, ventricular arrhythmia and local injection anesthesia. The committee delayed a decision on whether a lidocaine package insert should be required to discuss the animal carcinogenicity data pending final results of the liver slice study. Not all specimens have yet been examined in the liver slice study, which is expected to be complete in a few months and published in the fall. FDA is expected to use the findings to determine what actions to take, if any, on lidocaine-containing products. Industry has maintained that rat carcinogenicity data are not applicable to humans. |