Dosage form Design for Improvement of Bioavailability of Levodopa V: Absorption and Metabolism of Levodopa in Intestinal Segments of Dogs

Plasma levels of levodopa, total dopamine, and residual amounts of levodopa and its metabolites at the administered site were analyzed following administration of single 100-mg doses of levodopa in solution into isolated segments of the duodenum, jejunum, and ileum of the dog. The largest area under the plasma concentration-time curve (AUC) of levodopa during the 1.0-hr study was obtained following administration in the duodenum, followed by the jejunum and ileum. In addition, the residual amounts of levodopa and its metabolites detected at the administration sites were: ileum, 23%; jejunum, 7%; and duodenum, <1%. The largest AUC of total dopamine was obtained following administration in the jejunum, followed by the ileum and duodenum. This order was consistent with the order of levodopa decarboxylase enzyme activity reported previously. Therefore, it can be concluded that the major absorption site of levodopa in the intestine resides in the upper small intestine. Levodopa in 10-, 50-, and 100-mg doses was administered into isolated duodenal segments. The AUC of levodopa increased nonlinearly with increasing dose. Negligible amounts of both levodopa and its metabolites were observed in the segment at 1.0 hr after administration, indicating that the duodenal absorption of levodopa was not saturable within the dose range tested.