CONCURRENT ADMINISTRATION OF D-PENICILLAMINE AND ZINC HAS NO ADVANTAGES OVER THE USE OF EITHER SINGLE-AGENT ON COPPER EXCRETION IN THE RAT

The present study was conducted to examine in rats whether the combine d use of D-penicillamine (DPA) and a zinc salt, or the administration of a DPA!Zn complex could have some advantages over the use of either single agent on the excretion of copper. In a first experiment, three groups of adult male Sprague-Dawley rats were given by gavage one of t he following treatments for 5 days: 0.5 mmol/kg/day of DPA, 0.046 mmol /kg/day of zinc acetate dihydrate, and 0.5 mmol/kg/day of DPA plus 0.0 46 mmol/kg/day of zinc acetate dihydrate. A fourth group of rats (cont rol group) received deionized water during the same period. An increas e in the urinary excretion of copper was observed following DPA treatm ent, which continued for at least 5 days after the administration of t his compound was stopped. The amount of copper present in the feces: i ncluding that in the diet, was approximately 60 times greater than tha t normally present in control urines. During the period of zinc acetat e administration, the amount of copper in the feces was slightly, but significantly greater than that during control, D-penicillamine, or D- penicillamine plus zinc acetate administration. No differences between the treated groups and the control group were found in brain, liver, kidney and spleen concentrations of rats 5 days after the end of the t reatment period. In a second experiment, a similar comparison between D-penicillamine and sodium bis(3-mercapto-D-valinato)zinc hexahydrate (Na-2[Zn(DPA)(2)]. 6H(2)O), both given by gavage, also showed no signi ficant differences in the urinary excretion of copper in rats. (C) 199 8 Elsevier Science Ireland Ltd. All rights reserved.