Effects of Chronic Oral Administration on the Disposition of Laevodopa and its Major Metabolites in the Plasma of the Rat

Abstract

1. Plasma levels of total radioactivity, unchanged laevodopa, catecholamines, 3-O-methyldopa and non-amino phenolic acids were measured in rats treated orally with [³H]laevodopa (100 mg/kg, 100 μCi/kg) for different periods of time.

2. Chronic oral administration of laevodopa for two months significantly delayed the appearance of peak plasma levels and decreased the overall plasma concentrations of the unchanged drug as compared to controls. The extent of absorption of an oral dose of [³H]laevodopa was not significantly impaired on chronic treatment and/or ageing. The decrease in the levels of unchanged laevodopa appeared to be due to an increase in the apparent volumes of distribution of the drug and its metabolites upon ageing.

3. The plasma levels of the catecholamine metabolite fraction, which included dopamine, noradrenaline, etc., were much higher in chronically dosed animals.

4. These findings may be relevant in the understanding of such clinical observations as decreasing therapeutic effects and increasing toxicity after longterm laevodopa treatment in human patients