Description

Simple

A medication used to treat Parkinson's disease and other conditions similar to Parkinson's disease.

Clinical

A dopamine precursor used in the management of Parkinson's disease, often in combination with carbidopa, as well as other conditions associated with parkinsonism.

Overview

Levodopa is a prodrug of dopamine that is administered to patients with Parkinson's due to its ability to cross the blood-brain barrier[Label]. Levodopa can be metabolised to dopamine on either side of the blood-brain barrier and so it is generally administered with a dopa decarboxylase inhibitor like carbidopa to prevent metabolism until after it has crossed the blood-brain barrier[Label,1]. Once past the blood-brain barrier, levodopa is metabolized to dopamine and supplements the low endogenous levels of dopamine to treat symptoms of Parkinson's[Label]. The first developed drug product that was approved by the FDA was a levodopa and carbidopa combined product called Sinemet that was approved on May 2, 1975[1,7].

Pharmacology

Indication

Levodopa on its own is formulated as an oral inhalation powder indicated for intermittent treatment of off episodes in Parkinson's patients who are already being treated with carbidopa and levodopa[FDA Label]. Levodopa is most commonly formulated as an oral tablet with a peripheral dopa decarboxylas... Read more

Pharmacodynamic

Levodopa is able to cross the blood-brain barrier while dopamine is not[FDA Label,8]. The addition of a peripheral dopa decarboxylase inhibitor prevents the conversion of levodopa to dopamine in the periphery so that more... Read more

Mechanism of action

Levodopa by various routes crosses the blood brain barrier, is decarboxylated to form dopamine[Label,8]. This supplemental dopamine performs the role that endogenous dopamine cannot due to a decrease of natural concentrat... Read more

Absorption

Orally inhaled levodopa reaches a peak concentration in 0.5 hours with a bioavailability than is 70% that of the immediate release levodopa tablets with a peripheral dopa decarboxylase inhibitor like carbidopa or benserazide[Label, Read more

Protein binding

Levodopa binding to plasma proteins is negligible[ Read more

Volume of distribution

168L for orally inhaled levodopa[Label].

Clearance

Intravenously administered levodopa is cleared at a rate of 14.2mL/min/kg in elderly patients and 23.4mL/min/kg in younger patients[ Read more

Half life

2.3 hours for orally inhaled levodopa[FDA Label]. Oral levodopa has a half life of 50 minutes but when combined with a peripheral dopa decarboxylase inhibitor, the half life is increased to 1.5 hours[8].

Route of elimination

After 48 hours, 0.17% of an orally administered dose is recovered in stool, 0.28% is exhaled, and 78.4% is recovered in urine[ Read more

Toxicity

There is no readily available data for the use of levodopa in pregnancy[Label]. Rabbits treated with levodopa and carbidopa produced smaller litters and their offspring developed visceral and skeletal deformities[Label]. Levodopa may lower prolactin and interfere with lactation but there is limited... Read more

Adverse Effects

Contraindications

  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: History of Numerous Skin Cancers
      • Drugbank Id: DBCOND0070189
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Skin Lesion
      • Drugbank Id: DBCOND0037061
  • Recommended Actions:
    • Discontinue MAO inhibitors, except for selective MAO-B inhibitors, at least two weeks prior to levodopa therapy.
  • Regions: US
  • With Categories Coadmin:
      • Name: Monoamine Oxidase Inhibitors
      • Drugbank Id: DBCAT001004
      • Mesh Id: D008996
  • Regions: US
  • Patient Conditions:
      • Name: Narrow-angle glaucoma
      • Drugbank Id: DBCOND0095646

Food Interactions

    Information currently not available.

Interactions

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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
2,5-Dimethoxy-4-ethylamphetamine
The risk or severity of serotonin syndrome can be increased when Levodopa is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine
The risk or severity of adverse effects can be increased when Levodopa is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamine
The risk or severity of adverse effects can be increased when Levodopa is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-Methoxyamphetamine
The risk or severity of adverse effects can be increased when Levodopa is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine
The risk or severity of adverse effects can be increased when Levodopa is combined with 5-methoxy-N,N-dimethyltryptamine.
7-Nitroindazole
The risk or severity of adverse effects can be increased when Levodopa is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
The risk or severity of adverse effects can be increased when Levodopa is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
Acebutolol
The risk or severity of hypotension and orthostatic hypotension can be increased when Acebutolol is combined with Levodopa.
Acepromazine
The risk or severity of adverse effects can be increased when Levodopa is combined with Acepromazine.
Aceprometazine
The risk or severity of adverse effects can be increased when Levodopa is combined with Aceprometazine.
Acetazolamide
The risk or severity of adverse effects can be increased when Acetazolamide is combined with Levodopa.
Acetophenazine
The risk or severity of adverse effects can be increased when Acetophenazine is combined with Levodopa.
Acetylglycinamide chloral hydrate
The risk or severity of adverse effects can be increased when Levodopa is combined with Acetylglycinamide chloral hydrate.
Aclidinium
The absorption of Levodopa can be decreased when combined with Aclidinium.
Adinazolam
The risk or severity of adverse effects can be increased when Adinazolam is combined with Levodopa.
Adipiplon
The risk or severity of adverse effects can be increased when Levodopa is combined with Adipiplon.
Agomelatine
The risk or severity of adverse effects can be increased when Levodopa is combined with Agomelatine.
Ajulemic acid
The risk or severity of adverse effects can be increased when Ajulemic acid is combined with Levodopa.
Alaproclate
The risk or severity of adverse effects can be increased when Levodopa is combined with Alaproclate.
Alcuronium
The risk or severity of adverse effects can be increased when Levodopa is combined with Alcuronium.
8 References
  1. 1 . Djamshidian A, Poewe W: Apomorphine and levodopa in Parkinson's disease: Two revolutionary drugs from the 1950's. Parkinsonism Relat Disord. 2016 Dec;33 Suppl 1:S9-S12. doi: 10.1016/j.parkreldis.2016.12.004. Epub 2016 Dec 22.PubMed: 28012951
  2. 2 . Meiser J, Weindl D, Hiller K: Complexity of dopamine metabolism. Cell Commun Signal. 2013 May 17;11(1):34. doi: 10.1186/1478-811X-11-34.PubMed: 23683503
  3. 3 . Elroby SA, Makki MS, Sobahi TR, Hilal RH: Toward the understanding of the metabolism of levodopa I. DFT investigation of the equilibrium geometries, acid-base properties and levodopa-water complexes. Int J Mol Sci. 2012;13(4):4321-39. doi: 10.3390/ijms13044321. Epub 2012 Apr 2.PubMed: 22605980
  4. 4 . Robertson DR, Wood ND, Everest H, Monks K, Waller DG, Renwick AG, George CF: The effect of age on the pharmacokinetics of levodopa administered alone and in the presence of carbidopa. Br J Clin Pharmacol. 1989 Jul;28(1):61-9.PubMed: 2775615
  5. 5 . Abrams WB, Coutinho CB, Leon AS, Spiegel HE: Absorption and metabolism of levodopa. JAMA. 1971 Dec 27;218(13):1912-4.PubMed: 5171067
  6. 6 . Fanali G, Rampoldi V, di Masi A, Bolli A, Lopiano L, Ascenzi P, Fasano M: Binding of anti-Parkinson's disease drugs to human serum albumin is allosterically modulated. IUBMB Life. 2010 May;62(5):371-6. doi: 10.1002/iub.317.PubMed: 20225277
  7. 7 . FDA Approved Drug Products: Sinemet Link
  8. 8 . Sinemet FDA Label File