Metabolic Studies and Clinical Observations During L-Dopa Treatment of Parkinson's Disease

Abstract

Summary: Twenty-two patients with. Parkinson's disease were treated for the periods, of up to six months with L-dopa. In nine of the male patients metabolic observations were made after oral administration of '4C-L-dopa.Peak serum levels of total radioactivity represented small fractions of the dose given and occurred at one to two hours after ingestion. Two-thirds of the dose was excreted as metabolites in urine in eight hours. Insignificant fractions of the dose were excreted in stool and expired air. These results indicate rapid and complete absorption from the gastrointestinal tract, as well as rapid distribution and excretion. Clinical observations confirmed that i-dopa is an effective treatment for Parkinson's disease. Improvements in disability averaged 47% at 30 days, 55% at 50 days, and 60% at three months. Degree of improvement tended to be inversely related to age of patient, duration of illness, and severity of disease. Side-effects were seen in most patients, but were always reversible with dose reduction. Nausea was the chief dose-limiting side-effects in early therapy and choreoathetosis after two months of treatment. The average tolerated daily dose was 3 g. On the basis of this experience it seems that the drug can be used safely and effectively on an outpatient basis provided that dosage increments are introduced gradually, maximum dosage is limited to 4 g. a day, and supervision is both close and continuous.

Effect of Age and Arteriosclerosis on the Response of Parkinsonian Patients to Levodopa

“…Two patients aged less than 65, however, continued to show increasing benefit up to 12 months of continuous treatment. This finding confirms the observations of Yahr, Duvoisin, Hoehn, Schear, and Barrett (1968) and Peaston and Bianchine (1970). No patient who ultimately benefited from treatment with levodopa has failed to show improvement before the threemonth evaluation.…”

“…Two patients with arteriosclerotic Parkinsonism failed to show any response to treatment with levodopa. Cotzias et al (1969) were unable to find any correlation between age or arteriosclerosis and response to levodopa but subsequent workers have shown that degree of improvement is inversely related to both age (Peaston and Bianchine, 1970) and hypertension (Hughes, Polgar, Weightman, and Walton, 1971). Our results suggest that elderly or arteriosclerotic patients suffering from a Parkinsonian syndrome respond less well to levodopa than patients who show uncomplicated features of idiopathic Parkinsonism.…”

L-dopa treatment failure: explanation and correction.

“…It would nevertheless appear that under the experimental conditions described exposure to ultrasound does produce appreciable damage to human chromosomes. , 1970, 4, 93-94 The efficacy of L-3, 4,dihydroxyphenylalanine (L-dopa) in most patients with Parkinson's disease has been documented repeatedly (Calne et al, 1969;Cotzias et al, 1969;Mawdsley, 1970;Peaston and Bianchine, 1970a). Little is known, however, about the significant number of patients who do not respond (20-30%).…”

Levodopa pharmacokinetics -from stomach to brain : A study on patients with Parkinson’s disease

“…Very low levels of orally administrated levodopa are excreted in faeces indicating a high absorption of levodopa (41,42). When taken orally C max of levodopa in blood is seen after 1-2 hours (41,43) and levodopa is mainly excreted via the kidneys with two-thirds elimination within 8 hours (41) and 85 % elimination within 24 h (43). Only app.…”