Effect of chronic levodopa treatment on pyridoxine metabolism

Pyridoxine metabolism was investigated in eight chronic levodopa-treated parkinsonian patients and in eight matched dopa-naive controls by measurement of plasma and erythrocyte pyridoxal-5-phosphate concentrations over a 24-hour period, following intravenous administration of pyridoxine. After both a 10 mg and 100 mg pyridoxine dosage, plasma and erythrocyte pyridoxal-5-phosphate concentrations were significantly higher in the chronic levodopa-treated group than in the controls. The percentage change in pyridoxal-5-phosphate concentrations as a function of the administered doses of pyridoxine was greater in the dopa-treated group. Chronic administration of levodopa may result in an adaptive alteration in the decarboxylase system with an increased cellular ability to synthesize pyridoxal-5-phosphate from pyridoxine, possibly through enzyme induction. This metabolic alteration would protect against pyridoxine deficiency states and may explain in part the progressive loss of levodopa effectiveness sometimes observed.