Penicillamine: Pharmacokinetics and differential effects on zinc and copper status in chicks

The pharmacokinetics of D(-)-penicillamine (PA) and the effects of PA on the nutritional status of Cu and Zn in chicks were studied. When administered by subcutaneous or intravenous injection, PA was eliminated from the plasma with biphasic kinetics: i.e., a fast (halftime: 6-7 min) and a slow (halftime: 52-55 min) component. The elimination of PA from the liver or pancreas showed only the slow (halftime: 42-46 min) component. When PA was administered orally, plasma PA concentrations responded over time in a bimodal pattern, but the maximal level was only one-fifth that achieved by injection. The subcutaneous injection of PA elicited differential, transient changes in the concentrations of Zn and Cu in the plasma: plasma Zn concentration was decreased, and plasma Cu concentration was increased. Analyses of urine collected from ureter-cannulated chicks showed that PA was rapidly excreted via that route, and that urinary PA excretion was associated with increased urinary excretion of both Zn and Cu. These results show that PA treatment can alter tissue distributions particularly of Zn and, to a lesser extent, of Cu.