Effect of penicillamine on serum iron.

In recent years there has been an increasing interest in toxic reactions to drugs, and a number of these have been reported following the treatment of Wilson's disease with penicillamine, particularly the D-L racemic mixture. Purified L-penicillamine has been shown to be a pyridoxine antimetabolite in rats (Kuchinskas and du Vigneaud, 1957; Kuchinskas, Hovarth, and du Vigneaud, 1957) and more recently evidence for this activity has been reported in man tTu, Blackwell and Lee, 1963). The nephrotic syndrome and renal failure have also been reported following the use of D-L penicillamine (Adams, Goldman, Maxwell and Latta, 1964; Yonis and Karp, 1963) and also bone-marrow depression (Sternlieb and Scheinberg, 1964). Originally Dpenicillamine was thought to be completely nontoxic but recently there have been suggestions that even this isomer, in large doses, can also act as a pyridoxine antagonist not only in rats* (Asatoor, 1964; Gibbs and Walshe, 1965) but also in man (Jaffe, Altman, and Merryman, 1964), though work in this laboratory (Gibbs and Walshe, 1965) does not support the latter observations. Surprisingly there has been little mention of the possible action of penicillamine depleting the body of other divalent cations besides copper, though zinc has received some attention (Schouwink, 1961). It has been shown that a significant fall in the serum copper occurs in patients with Wilson's disease after less than a year's treatment (J. M. Walshe, 1964, unpublished observations). Boulding mentioned the possibility of metal depletion (Boulding, 1961) and suggested that a 'trace metal cocktail' should be given weekly to all patients on maintenance doses of penicillamine. However, there are no published reports to suggest that this precept has been followed, and none of the reports on the use of penicillamine in the treatment of Wilson's disease have included any data on serum iron levels (Sternlieb and