The Antipyridoxine Effect of Penicillamine in Man*

Abstract

L-penicillamine was a pyridoxine antagonist in animals while the D-form was free of this effect. In view of the recent availability of the pure D-isomer for clinical use, it was deemed of interest to compare the anti-B6 effects of the 2 compounds in man. Pyridoxine metabolism was evaluated by measurement of the 24 hour urinary excretion of xanthurenic acid and kynurenine following a loading dose of 5 gm of DL tryptophane. Normal subjects and patients with rheumatoid arthritis were studied. Significant elevation in the excretion of these tryptophane metabolites was found after 14 days of D-penicill-amine at a dosage of 2 gm/day. DL-phenicillamine showed even a greater degree of anti-metabolite effect as measured by these parameters. In one patient, D-penicillamine exerted an effect comparable to 1200 mg/day of INH, based on the kynurenine values. In all instances, 100mg of pyridoxine by injection reversed the drug-induced abnormality. It is suggested that pyridoxine supplementation be included in any long-term penicillamine therapy, regardless of the isomer employed.