[Effects of D-penicillamine on vitamin B6 and metal ions in rats (author's transl)].

D-penicillamine, an antirheumatic drug having chelating ability, was investigated for the effects on vitamin B6 and metals at doses ranging from 25 to 600 mg per kg, p.o., or in case of the highest dosing of D-penicillamine, together with s.c. administration of cupric sulfate or pyridoxine hydrochloride for 28 days in rats. The effects were compared with the actions of L- and DL-penicillamine. D-penicillamine increased urinary vitamin B6 excretion and lowered vitamin B6 levels extensively in serum and slightly in the liver. Those changes were also seen with L- and DL-penicillamine. On the other hand, D-penicillamine had no effects on the activities of serum transaminases and alkaline phosphatase and on the urinary excretion of xanthurenic acid after a tryptophan loading. D-Penicillamine, like L- and DL-penicillamine increased the urinary excretion of Cu and Zn and reduced Cu contents both in serum and liver. When Cu was given s.c. concomitantly with D-penicillamine p.o., an enhancement was seen in the effects of D-penicillamine on the urinary excretion of xanthurenic acid and body weight gain, as well as on the serum level of vitamin B6 and serum transaminase activities. Simultaneous injection of vitamin B6 with D-penicillamine produced a recovery in the lowering vitamin B6 levels induced by D-penicillamine in serum and liver and enhanced the urinary excretion of Cu, but did not influence the serum content of Cu. Thus, although the antivitamin B6 activity of D-penicillamine was demonstrated in rats, the degree was slight and was less than that seen with L- or DL-penicillamine. Moreover, the enhancing effect of Cu on the antivitamin B6 activity of D-penicillamine might be explained by the chelate formation between D-penicillamine-pyridoxal complex and Cu.