Continuous oral administration of L-dihydroxyphenylalanine (L-DOPA) solution to patients with advanced Parkinson's disease.

Abstract

In six patients with advanced Parkinson's disease (PD), we have characterized the clinical responses and serum levels of DOPA and 3-O-methyldopa in response to continuous i.v., nasogastroduodenal (NGD), and oral (p.o.) administration of L-DOPA solution with concomitant suppression of peripheral decarboxylase activity by carbidopa. When compared to therapy with L-DOPA/carbidopa tablets, all patients experienced increased "on" and decreased "off" time with continuous L-DOPA intake. This improvement in mobility was accompanied by increases in duration and severity of dyskinesias. Serum levels of DOPA and 3-O-methyldopa were linearly related in ultrafiltered serum water compared to perchloric acid-treated serum samples, suggesting little protein binding. DOPA serum levels at which patients first turned "on" and those after several hours of continuous i.v. infusion clustered over a narrow range and were not predictable based on i.v. infusion rates, in spite of concomitant carbidopa intake. Continuous p.o. intake of L-DOPA solution produced serum levels of both DOPA and 3-O-methyldopa that were generally steady over the day and predictable based on L-DOPA intake rate. We conclude that "continuous" intake of L-DOPA solution orally, while cumbersome to and demanding of patients, can produce stable DOPA serum levels and approximate the improvement seen with continuous i.v. infusion. In our study, the apparent volume of distribution of L-DOPA was predictable with p.o. intake but not with i.v. administration of L-DOPA solution.