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Information about Levodopa

Levodopa (L-Dopa) is an amino acid precursor of dopamine and is the most effective and commonly used drug in the treatment of Parkinson disease.  

Liver safety of Levodopa

Levodopa is usually combined with carbidopa, which is an inhibitor of L-amino acid decarboxylase, the plasma enzyme that metabolizes levodopa peripherally.  Treatment with the combination of levodopa and carbidopa has been associated with mild and transient increases in serum enzymes in a proportion of patients and with very rare instances of clinically apparent acute liver injury.

Mechanism of action of Levodopa

Levodopa (lee" voe doe' pa) is a derivative of phenylalanine and is a metabolic precursor of dopamine.  Levodopa crosses the blood brain barrier where it is converted to dopamine by decarboxylation in the presynaptic terminals of dopaminergic neurons.  After release, it is transported back into the dopaminergic terminals or is metabolized either by catechol-O-methyltransferase (COMT) or by monoamine oxidase (MAO).  When given orally, levodopa is usually combined with carbidopa (kar' bi doe' pa), which is also a derivative of phenylalanine and is an inhibitor of L-amino acid decarboxylase, the plasma enzyme that metabolizes levodopa peripherally. 

FDA approval information for Levodopa

Levodopa was approved for use in the United States in 1970 and the combination of levodopa and carbidopa in 1975.  Levodopa, alone and in combination with carbodopa, remains a commonly used agent for Parkinson disease with more than 2 million prescriptions filled yearly in the United States. 

Clinical use of Levodopa

Current indications include therapy of symptomatic Parkinson disease as well as spastic disorders and extrapyramidal disorders due to medications.  Levodopa is available as tablets with various fixed combination with carbidopa (10-100, 25-100 and 25-250) in generic forms and under the trade name Sinemet.  The combination is typically given 3 to 4 times daily, although a controlled release form is available that allows for twice daily dosing.  The optimal dose varies by patient; it is typically started at a low dose and increased based upon clinical response and tolerance.  Side effects can include nausea, dyskinesias, hallucinations, confusion, postural hypotension, sedation, constipation, sleep disturbances, depression and hypersexuality – side effects that are common to all dopaminergic agents.

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