Levodopa Other names: L-dopa L-3,4-dihydroxyphenylalanine

Levodopa, the metabolic precursor of dopamine, crosses the blood-brain barrier and presumably is converted to dopamine in the brain. This is thought to be the mechanism whereby levodopa relieves symptoms of Parkinson’s disease.

There are no relevant data on the pharmacodynamic effects of levodopa.

In the presence of carbidopa, the pharmacokinetics of levodopa are dose-proportional in healthy subjects taking up to 84 mg of levodopa. In the presence of carbidopa, the terminal elimination half-life (t_1/2) of levodopa following a single administration of levodopa 84 mg was 2.3 hours.

Absorption

After a single dose of levodopa 84 mg (two 42 mg capsules), the median T_max for plasma levodopa was approximately 0.5 hours (range 0.17–2.00 hours). In fasted healthy volunteers the bioavailability of levodopa was approximately 70% relative to immediate-release oral levodopa tablets. The dose-normalized C_max of levodopa is approximately 50% of that following immediate-release oral tablets.

Distribution

Apparent volume of distribution (Vz/F) was 168 L for levodopa 84 mg.

Metabolism and Elimination

Levodopa is extensively metabolized, and the two major metabolic pathways are decarboxylation by dopa decarboxylase and O-methylation by catechol-O-methyltransferase (COMT).

Specific Populations

Geriatric Population

Clinical studies specifically designed to analyze the effects of age on the pharmacokinetics of levodopa were not conducted with levodopa.

Male and Female Patients

After a single dose administration of levodopa 84 mg, the body-weight adjusted C_max and AUC_0-24 were similar between women and men. No adjustment in dosage is required based on sex.

Hepatic/Renal Impairment

Levodopa has not been studied in patients with hepatic or renal impairment.

Smokers

In a pharmacokinetic study following a single administration of levodopa 84 mg dose in the presence of carbidopa, levodopa exposure (AUC and C_max) in smokers (N=25) and non-smokers (N=31) were similar.