(D)-PENICILLAMINE INCREASES HEPATIC OXALATE PRODUCTION RESULTING IN HYPEROXALURIA

Purpose: To determine whether (D)-penicillamine is effective in reduci ng hepatic oxalate production and urinary oxalate excretion. Materials and Methods: (D)-Penicillamine was administered orally to rats to det ermine its effect on urinary oxalate excretion and used in isolated ra t hepatocytes to investigate the effect of(D)-penicillamine on oxalate production from glycolate. Studies involving hepatic aminotransferase s and hepatocytes isolated from (D)-penicillamine treated rats were us ed to clarify the discrepancy between the in vitro and in vivo results . Results: In hepatocytes (D)-penicillamine lead to a significant redu ction in oxalate production from glycolate. In vivo however, (D)-penic illamine led to a significant increase in urinary oxalate excretion an d a decrease in plasma aminotransferase activity. Hepatic aminotransfe rases are involved in diverting oxalate precursors from oxalate produc tion. In vitro, (D)-penicillamine was shown to inhibit hepatic aminotr ansferases. Hepatocytes isolated from (D)-penicillamine-treated rats p roduced significantly more oxalate than controls. Conclusions: These r esults indicate that (D)-penicillamine increases hepatic oxalate produ ction and urinary oxalate excretion. (D)-penicillamine therefore has n o therapeutic potential for reducing endogenous oxalate production and urinary oxalate excretion. Moreover, in conditions such as Wilson's D isease which is often associated with hypercalcuria, its use may be co ntraindicated.