HYPERSENSITIVITY REACTIONS TO ANTHRANILIC ACID-DERIVATIVES

Anthranilic acid derivatives are a group of nonsteroidal antiinflammat ory drugs that include glafenine and fenamates. We report a woman who had immediate adverse reactions to glafenine and meclofenamate sodium. Skin prick and intradermal tests were performed with solutions of gla fenine and meclofenamate in phosphate-buffered saline (PBS) and with t he drugs bound to human serum albumin (HSA). Prick and intradermal tes ts with PBS solutions were negative for both drugs as were prick tests with HSA solutions. Intradermal tests with HSA-glafenine, however, we re positive at 20 minutes, and at 6 and 24 hours. Intradermal tests wi th HSA-meclofenamate elicited a positive response at 6 and 24 hours. T hese tests were negative when performed in control subjects. A leukocy te histamine release lest and a RAST assay were negative for both drug s. The patient was challenged following a double-blind placebo-control led oral procedure and tolerated therapeutic doses of aspirin, indomet hacin, ibuprofen, dipyrone, diclofenac, piroxicam, and acetaminophen. The oral challenge with glafenine and meclofenamate reproduced the rea ctions (eliciting doses: 50 mg and 15 mg, respectively), and the patie nt also reacted to 30 mg of mefenamic acid, an anthranilic acid deriva tive she had never previously received. This is an exceptional case of selective adverse reactions to glafenine and fenamates, anthranilic a cid derivatives, in a patient tolerating aspirin and other cyclooxygen ase inhibitors. Our study implicates an immunologic mechanism, and the existence of cross-reactivity between the drugs (or some active metab olite generated in vivo).