Metabolic patterns and clinical response to levodopa therapy in Parkinson's disease

Abstract

Longitudinal double‐blind case studies of two parkinsonian patients simultaneously treated with equal doses of levodopa are reported. The patients were alternately treated with placebo and levodopa in crossover design after an initial period of treatment with trihexyphenidyl. The metabolic fate of orally ingested levodopa was determined by measuring the urinary excretion of dopa and some of its maior metabolites. Neurological and clinical measurements were made on days of 24 hour urine collection. Intersubiect differences were noted in the excretion profiles of dopa and metabolites studied as well as in clinical response to gradually increasing dosage buildup of levodopa. The maior portion of ingested levodopa was recovered in urine in the form of the acidic metabolites DOPAC and HV A, with urinary HV A exceeding that of DOPAC. Prolonged treatment with levodopa resulted in increased DOPAC excretion relative to HVA. Ingestion of levodopa at 5 gm per day decreased mean 5‐HIAA excretion from placebo value by apprOXimately 50 %. Less than 1 % of levodopa dose was recovered in urine during a 24 hour period. Concomitantly, dopamine and norepinephrine excretion increased by approximately 10 and 100 fold from placebo phase, respectively. Trihexyphenidyl administration did not affect excretion of catecholamines or those metabolites that were studied.