Clinical pharmacokinetics of levodopa in parkinson's disease

Although levodopa has provided a major advance in the treatment of parkinsonism, its maximum benefits have not yet been realised, in part because of its complicated pharmacokinetics. This review summarises that available pharmacokinetic data involving levodopa, especially as it relates to therapeutic response of parkinsonian patients. A large number of factors, including protein intake, gastric emptying time, pyridoxine ingestion, and dopa decarboxylase activity, affect plasma levels of levodopa attained following oral administration of this drug. Other variables influence the rate of brain uptake of levodopa from the blood. Even so, plasma levodopa concentration correlates significantly with dosage size in a large parkinsonian population and also coincides with therapeutic response in many, but not all, patients. Therefore, in certain instances, valuable information may be derived by correlating clinical response with plasma levodopa concentration. Cerebrospinal fluid levels of homovanillic acid, a major metabolite of dopamine, may have some value in predicting clinical response to levodopa. This relationship, however, has not been firmly established. Concentration of homovanillic acid or levodopa in body fluids may also be closely related to certain adverse side-effects, including abnormal involuntary movements, gastric discomfort and psychiatric disturbances. Evidence indicates that a clearer understanding of levodopa pharmacokinetics may improve the clinical management of parkinsonism.