Influence of route of administration on physiological availability of levodopa in dogs.

The physiological basis for the reduced levodopa bioavailability following oral administration was investigated. Four dogs received single 25-mg/kg doses of 14C-levodopa on three separate occasions in a crossover fashion via hepatoportal catheter, intravenous, and oral administrations. Plasma and urine specimens were analyzed for intact levodopa and total radioactivity. The ratios of areas under the plasma concentration-time curves following hepatoportal and intravenous adminstrations were close to unity, and the shapes of the curves were virtually identical. Following oral administration, however, significant reductions in the areas under the plasma concentration-time curves were observed. These data indicate that the physiologically impaired bioavailability of orally administered levodopa occurs almost exclusively as a result of metabolic degradation within the GI lumen and/or gut wall.