Indications
Levodopa is primarily prescribed for the management of Parkinson's disease. It is also utilized in the treatment of post-encephalitic parkinsonism and symptomatic parkinsonism resulting from carbon monoxide or manganese intoxication. Typically, levodopa is administered as an oral tablet in conjunction with a peripheral dopa decarboxylase inhibitor, enhancing its efficacy. Additionally, levodopa is available as an oral inhalation powder specifically for the intermittent management of "off" episodes in patients with Parkinson's disease who are already receiving treatment with both carbidopa and levodopa.
Pharmacodynamics
Levodopa possesses the ability to traverse the blood-brain barrier, a characteristic not shared by dopamine. The co-administration of a peripheral dopa decarboxylase inhibitor is crucial as it inhibits the peripheral conversion of levodopa to dopamine, thereby ensuring a greater concentration of levodopa can cross into the central nervous system. Once within the brain, levodopa undergoes conversion to dopamine by the enzyme aromatic-L-amino-acid decarboxylase, effectively replenishing the diminished dopamine levels characteristic of Parkinson's disease.
Absorption
When administered as an orally inhaled formulation, levodopa reaches its peak plasma concentration within 0.5 hours. The bioavailability of this inhaled form is approximately 70% compared to immediate-release oral tablets that are combined with peripheral dopa decarboxylase inhibitors such as carbidopa or benserazide. This rapid absorption profile is advantageous for managing acute "off" episodes in Parkinson's patients.
Metabolism
Upon administration, levodopa undergoes metabolism via two primary pathways. It can be converted to dopamine by aromatic-L-amino-acid decarboxylase or can be O-methylated to form 3-O-methyldopa via catechol-O-methyltransferase. The latter, 3-O-methyldopa, does not proceed to form dopamine. Once levodopa is metabolized to dopamine, it is further processed into various metabolites, such as sulfated or glucuronidated derivatives, epinephrine, or homovanillic acid. The primary metabolic byproducts include 3,4-dihydroxyphenylacetic acid, comprising 13-47% of metabolites, and homovanillic acid, accounting for 23-39%.
Mechanism of Action
Levodopa effectively crosses the blood-brain barrier through various administration routes and undergoes decarboxylation to produce dopamine. This exogenous dopamine compensates for the reduced levels of naturally occurring dopamine and activates dopaminergic receptors.
