Temporal relationships between plasma and cerebrospinal fluid pharmacokinetics of levodopa and clinical effect in Parkinson's disease.

We studied the pharmacokinetics of levodopa and its metabolites in plasma and ventricular cerebrospinal fluid in 4 parkinsonian patients with indwelling Ommaya reservoirs placed at the time of previous adrenal-medullary to caudate nucleus transplantation. Cerebrospinal fluid levodopa levels were 11.9% of those in plasma. Motor performance and dyskinesia correlated more closely with the time course of the appearance of levodopa in the ventricular cerebrospinal fluid than with the plasma levodopa concentration and did not correlate with plasma 3-O-methyldopa or cerebrospinal fluid 3-O-methyldopa or homovanillic acid. Our data confirm that the wearing off of the levodopa effect in patients with advanced Parkinson's disease is a function of drug concentration in the central nervous system.