[Effect of D-penicillamine on vitamine B6 and collagen metabolism (author's transl)]

Although D-Penicillamine (D-PeA) administration is getting popular in the treatment of rheumatoid arthritis (RA), the mechanism by which D-PeA produced therapeutic effect has not been fully elucidated. D-PeA had been shown to exert an antivitamine B6 effect. However, it has not been precisely confirmed if clinical dose of D-PeA induces vitamine B6 (VB6) deficiency. In order to clarify these questions, biochemical analyses of bone and skin collagens and determination of VB6 content in soft tissues have been performed in the rats administrated therapeutic dose of D-PeA. VB6 deficiency was not observed in the brain and skin from rats fed on normal diet containing D-PeA (13.0--33.5 mg/kg wt). There were no significant changes in the stability of collagen from bone and skin. On the other hand, significant VB6 deficiency and reduced stability of collagen were observed in rats fed on VB6 deficient diet containing the same amount of D-PeA. Aldehyde formation of collagen molecule and cross-link formation of collagen were also found to be suppressed. The same results were obtained from analyses in rats fed on VB6 deficient diet without D-PeA administration. These data indicate that D-PeA is not capable of producing VB6 deficiency in the dosage employed in patients. However, in the treatment for patients who are not taking enough nutrition, the possibility of VB6 deficiency can not be neglected. Once VB6 deficiency is induced by D-PeA administration, severe connective tissue disorder may be produced, since VB6 is required for enzymic activity of lysyl oxidase. It is unlikely that the therapeutic effects of D-PeA in the treatment of RA are produced the the disturbance of collagen cross-link formation as discussed before. Immunologic reactions of D-PeA may play more important role in the improvement of clinical symptoms of this disease.