The antipyridoxine effect of penicillamine in

Penicillamine is a potent oral chelating agent that is used in the treatment of Wilson's disease and certain heavy metal intoxications (1, 2). It is currently under study in primary macroglobu-linemia, the cold agglutinin syndrome, rheumatoid arthritis, and cystinuria (3-6). It has been well established that L-penicillamine exerts an anti-vitamin B6 effect in the rat (7, 8). This is mani-fest by growth depression, excessive urinary ex-cretion of xanthurenic acid after a tryptophane load, and a reduced activity of the pyridoxine-de-pendent alanine-glutamic (G.P.T.) and aspartic-glutamic (G.O.T.) transaminases. All of these effects were reversed by the simultaneous adminis-tration of vitamin B6. D-Penicillamine was not growth inhibitory in the rat, hence it has been be-lieved to be devoid of antipyridoxine activity (9). L-Penicillamine forms a thiazolidine compound with pyridoxal 5-phosphate (10). Since pyri-doxal 5-phosphate is the coenzyme of kynureninase (11), its inactivation by L-penicillamine would re-sult in an impairment in the metabolism of tryp-tophane via the kynurenine pathway (7). Re-cent studies, however, indicate that D-penicillamine also forms a thiazolidine with pyridoxal 5-phos-phate (12); hence it too might be expected to have antivitamin B6 effects. The increased urinary excretion of the inter-mediary metabolites of tryptophane (xanthurenic acid and kynurenine) that occurs in patients treated with isoniazid has led to the concept that that drug is a metabolic antagonist of vitamin B, (13). The co-administration of this vitamin with isoniazid has favorably influenced certain of the toxic manifestations of the drug without impairing its efficacy (14). DL-Penicillamine has l)een employed clinically without the apparent development of signs of py-* Submitted for publication April 21, 1964; accepte