Peringatan Keamanan

There is no readily available data for the use of levodopa in pregnancyLabel. Rabbits treated with levodopa and carbidopa produced smaller litters and their offspring developed visceral and skeletal deformitiesLabel. Levodopa may lower prolactin and interfere with lactation but there is limited human data to demonstrate this effectLabel. Levodopa is present in human breast milk and so the potential effects of nursing while taking levodopa should be considered before prescribing levodopa to nursing mothersLabel. There is currently a lack of data on the safety and effectiveness of using levodopa in pediatric patientsLabel. Patients over 65 years of age are more likely to experience adverse effects associated with taking levodopa, however this generally is not sufficient to exclude this patient group from treatmentLabel.

Levodopa

DB01235

small molecule approved

Deskripsi

Levodopa is a prodrug of dopamine that is administered to patients with Parkinson's due to its ability to cross the blood-brain barrierLabel. 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 barrierLabel,A177781. Once past the blood-brain barrier, levodopa is metabolized to dopamine and supplements the low endogenous levels of dopamine to treat symptoms of Parkinson'sLabel. 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, 1975A177781,L6133.

Struktur Molekul 2D

Berat 197.1879
Wujud solid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (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[F4579].
Volume Distribusi 168L for orally inhaled levodopa[Label].
Klirens (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[A177802]. When given carbidopa, the clearance of levodopa was 5.8mL/min/kg in elderyly patients and 9.3mL/min/kg in younger patients[A177802].

Absorpsi

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 benserazideLabel,A177781.

Metabolisme

Levodopa is either converted to dopamine by aromatic-L-amino-acid decarboxylase or O-methylated to 3-O-methyldopa by catechol-O-methyltransferaseLabel,A177745,A177733. 3-O-methyldopa cannot be metabolized to dopamineA177733. Once levodopa is converted to dopamine, it is converted to sulfated or glucuronidated metabolites, epinephrine E, or homovanillic acid through various metabolic processesA177745. The primary metabolites are 3,4-dihydroxyphenylacetic acid (13-47%) and homovanillic acid (23-39%)A177733,A177805.

Rute Eliminasi

After 48 hours, 0.17% of an orally administered dose is recovered in stool, 0.28% is exhaled, and 78.4% is recovered in urineA177805

Interaksi Makanan

2 Data
  • 1. Avoid multivalent ions. Iron salts may reduce levodopa absorption.
  • 2. Take with or without food. A diet high in protein may delay absorption and AUC of levodopa.

Interaksi Obat

1019 Data
Duloxetine The risk or severity of orthostatic hypotension and syncope can be increased when Levodopa is combined with Duloxetine.
Aldesleukin The risk or severity of hypotension and orthostatic hypotension can be increased when Aldesleukin is combined with Levodopa.
Streptokinase The risk or severity of hypotension and orthostatic hypotension can be increased when Streptokinase is combined with Levodopa.
Valsartan The risk or severity of hypotension and orthostatic hypotension can be increased when Valsartan is combined with Levodopa.
Ramipril The risk or severity of hypotension and orthostatic hypotension can be increased when Ramipril is combined with Levodopa.
Esmolol The risk or severity of hypotension and orthostatic hypotension can be increased when Esmolol is combined with Levodopa.
Betaxolol The risk or severity of hypotension and orthostatic hypotension can be increased when Betaxolol is combined with Levodopa.
Reserpine The risk or severity of hypotension and orthostatic hypotension can be increased when Reserpine is combined with Levodopa.
Torasemide The risk or severity of hypotension and orthostatic hypotension can be increased when Torasemide is combined with Levodopa.
Methyclothiazide The risk or severity of hypotension and orthostatic hypotension can be increased when Methyclothiazide is combined with Levodopa.
Metoprolol The risk or severity of hypotension and orthostatic hypotension can be increased when Metoprolol is combined with Levodopa.
Ropinirole The risk or severity of hypotension and orthostatic hypotension can be increased when Ropinirole is combined with Levodopa.
Isradipine The risk or severity of hypotension and orthostatic hypotension can be increased when Isradipine is combined with Levodopa.
Olmesartan The risk or severity of hypotension and orthostatic hypotension can be increased when Olmesartan is combined with Levodopa.
Morphine The risk or severity of hypotension and orthostatic hypotension can be increased when Morphine is combined with Levodopa.
Ropivacaine The risk or severity of hypotension and orthostatic hypotension can be increased when Ropivacaine is combined with Levodopa.
Bupivacaine The risk or severity of hypotension and orthostatic hypotension can be increased when Bupivacaine is combined with Levodopa.
Chlorthalidone The risk or severity of hypotension and orthostatic hypotension can be increased when Chlorthalidone is combined with Levodopa.
Tolcapone The risk or severity of hypotension and orthostatic hypotension can be increased when Tolcapone is combined with Levodopa.
Nitroprusside The risk or severity of hypotension and orthostatic hypotension can be increased when Nitroprusside is combined with Levodopa.
Atenolol The risk or severity of hypotension and orthostatic hypotension can be increased when Atenolol is combined with Levodopa.
Diltiazem The risk or severity of hypotension and orthostatic hypotension can be increased when Diltiazem is combined with Levodopa.
Minoxidil The risk or severity of hypotension and orthostatic hypotension can be increased when Minoxidil is combined with Levodopa.
Timolol The risk or severity of hypotension and orthostatic hypotension can be increased when Timolol is combined with Levodopa.
Amlodipine The risk or severity of hypotension and orthostatic hypotension can be increased when Amlodipine is combined with Levodopa.
Triamterene The risk or severity of hypotension and orthostatic hypotension can be increased when Triamterene is combined with Levodopa.
Nimodipine The risk or severity of hypotension and orthostatic hypotension can be increased when Nimodipine is combined with Levodopa.
Nisoldipine The risk or severity of hypotension and orthostatic hypotension can be increased when Nisoldipine is combined with Levodopa.
Pramipexole The risk or severity of hypotension and orthostatic hypotension can be increased when Pramipexole is combined with Levodopa.
Spironolactone The risk or severity of hypotension and orthostatic hypotension can be increased when Spironolactone is combined with Levodopa.
Nitric Oxide The risk or severity of hypotension and orthostatic hypotension can be increased when Nitric Oxide is combined with Levodopa.
Bendroflumethiazide The risk or severity of hypotension and orthostatic hypotension can be increased when Bendroflumethiazide is combined with Levodopa.
Prazosin The risk or severity of hypotension and orthostatic hypotension can be increased when Prazosin is combined with Levodopa.
Nabilone The risk or severity of hypotension and orthostatic hypotension can be increased when Nabilone is combined with Levodopa.
Sotalol The risk or severity of hypotension and orthostatic hypotension can be increased when Sotalol is combined with Levodopa.
Fosinopril The risk or severity of hypotension and orthostatic hypotension can be increased when Fosinopril is combined with Levodopa.
Trandolapril The risk or severity of hypotension and orthostatic hypotension can be increased when Trandolapril is combined with Levodopa.
Metolazone The risk or severity of hypotension and orthostatic hypotension can be increased when Metolazone is combined with Levodopa.
Lercanidipine The risk or severity of hypotension and orthostatic hypotension can be increased when Lercanidipine is combined with Levodopa.
Benazepril The risk or severity of hypotension and orthostatic hypotension can be increased when Benazepril is combined with Levodopa.
Propranolol The risk or severity of hypotension and orthostatic hypotension can be increased when Propranolol is combined with Levodopa.
Enalapril The risk or severity of hypotension and orthostatic hypotension can be increased when Enalapril is combined with Levodopa.
Doxazosin The risk or severity of hypotension and orthostatic hypotension can be increased when Doxazosin is combined with Levodopa.
Amiloride The risk or severity of hypotension and orthostatic hypotension can be increased when Amiloride is combined with Levodopa.
Labetalol The risk or severity of hypotension and orthostatic hypotension can be increased when Labetalol is combined with Levodopa.
Thiopental The risk or severity of hypotension and orthostatic hypotension can be increased when Thiopental is combined with Levodopa.
Bisoprolol The risk or severity of hypotension and orthostatic hypotension can be increased when Bisoprolol is combined with Levodopa.
Clofarabine The risk or severity of hypotension and orthostatic hypotension can be increased when Clofarabine is combined with Levodopa.
Dexmedetomidine The risk or severity of hypotension and orthostatic hypotension can be increased when Dexmedetomidine is combined with Levodopa.
Mecamylamine The risk or severity of hypotension and orthostatic hypotension can be increased when Mecamylamine is combined with Levodopa.
Verapamil The risk or severity of hypotension and orthostatic hypotension can be increased when Verapamil is combined with Levodopa.
Losartan The risk or severity of hypotension and orthostatic hypotension can be increased when Losartan is combined with Levodopa.
Thioridazine The risk or severity of hypotension and orthostatic hypotension can be increased when Thioridazine is combined with Levodopa.
Amphotericin B The risk or severity of hypotension and orthostatic hypotension can be increased when Amphotericin B is combined with Levodopa.
Moexipril The risk or severity of hypotension and orthostatic hypotension can be increased when Moexipril is combined with Levodopa.
Phentolamine The risk or severity of hypotension and orthostatic hypotension can be increased when Phentolamine is combined with Levodopa.
Furosemide The risk or severity of hypotension and orthostatic hypotension can be increased when Furosemide is combined with Levodopa.
Tizanidine The risk or severity of hypotension and orthostatic hypotension can be increased when Tizanidine is combined with Levodopa.
Eplerenone The risk or severity of hypotension and orthostatic hypotension can be increased when Eplerenone is combined with Levodopa.
Methazolamide The risk or severity of hypotension and orthostatic hypotension can be increased when Methazolamide is combined with Levodopa.
Tamsulosin The risk or severity of hypotension and orthostatic hypotension can be increased when Tamsulosin is combined with Levodopa.
Sufentanil The risk or severity of hypotension and orthostatic hypotension can be increased when Sufentanil is combined with Levodopa.
Apomorphine The risk or severity of hypotension and orthostatic hypotension can be increased when Apomorphine is combined with Levodopa.
Lisinopril The risk or severity of hypotension and orthostatic hypotension can be increased when Lisinopril is combined with Levodopa.
Nitroglycerin The risk or severity of hypotension and orthostatic hypotension can be increased when Nitroglycerin is combined with Levodopa.
Mannitol The risk or severity of hypotension and orthostatic hypotension can be increased when Mannitol is combined with Levodopa.
Isoflurane The risk or severity of hypotension and orthostatic hypotension can be increased when Isoflurane is combined with Levodopa.
Hydroflumethiazide The risk or severity of hypotension and orthostatic hypotension can be increased when Hydroflumethiazide is combined with Levodopa.
Perindopril The risk or severity of hypotension and orthostatic hypotension can be increased when Perindopril is combined with Levodopa.
Candesartan cilexetil The risk or severity of hypotension and orthostatic hypotension can be increased when Candesartan cilexetil is combined with Levodopa.
Tolazoline The risk or severity of hypotension and orthostatic hypotension can be increased when Tolazoline is combined with Levodopa.
Fenoldopam The risk or severity of hypotension and orthostatic hypotension can be increased when Fenoldopam is combined with Levodopa.
Indapamide The risk or severity of hypotension and orthostatic hypotension can be increased when Indapamide is combined with Levodopa.
Propofol The risk or severity of hypotension and orthostatic hypotension can be increased when Propofol is combined with Levodopa.
Conivaptan The risk or severity of hypotension and orthostatic hypotension can be increased when Conivaptan is combined with Levodopa.
Eprosartan The risk or severity of hypotension and orthostatic hypotension can be increased when Eprosartan is combined with Levodopa.
Chlorothiazide The risk or severity of hypotension and orthostatic hypotension can be increased when Chlorothiazide is combined with Levodopa.
Quinapril The risk or severity of hypotension and orthostatic hypotension can be increased when Quinapril is combined with Levodopa.
Isosorbide dinitrate The risk or severity of hypotension and orthostatic hypotension can be increased when Isosorbide dinitrate is combined with Levodopa.
Bumetanide The risk or severity of hypotension and orthostatic hypotension can be increased when Bumetanide is combined with Levodopa.
Remifentanil The risk or severity of hypotension and orthostatic hypotension can be increased when Remifentanil is combined with Levodopa.
Etacrynic acid The risk or severity of hypotension and orthostatic hypotension can be increased when Etacrynic acid is combined with Levodopa.
Levosimendan The risk or severity of hypotension and orthostatic hypotension can be increased when Levosimendan is combined with Levodopa.
Phenoxybenzamine The risk or severity of hypotension and orthostatic hypotension can be increased when Phenoxybenzamine is combined with Levodopa.
Pindolol The risk or severity of hypotension and orthostatic hypotension can be increased when Pindolol is combined with Levodopa.
Telmisartan The risk or severity of hypotension and orthostatic hypotension can be increased when Telmisartan is combined with Levodopa.
Methyldopa The risk or severity of hypotension and orthostatic hypotension can be increased when Methyldopa is combined with Levodopa.
Dipyridamole The risk or severity of hypotension and orthostatic hypotension can be increased when Dipyridamole is combined with Levodopa.
Hydrochlorothiazide The risk or severity of hypotension and orthostatic hypotension can be increased when Hydrochlorothiazide is combined with Levodopa.
Levobupivacaine The risk or severity of hypotension and orthostatic hypotension can be increased when Levobupivacaine is combined with Levodopa.
Guanfacine The risk or severity of hypotension and orthostatic hypotension can be increased when Guanfacine is combined with Levodopa.
Isosorbide mononitrate The risk or severity of hypotension and orthostatic hypotension can be increased when Isosorbide mononitrate is combined with Levodopa.
Felodipine The risk or severity of hypotension and orthostatic hypotension can be increased when Felodipine is combined with Levodopa.
Irbesartan The risk or severity of hypotension and orthostatic hypotension can be increased when Irbesartan is combined with Levodopa.
Nitrendipine The risk or severity of hypotension and orthostatic hypotension can be increased when Nitrendipine is combined with Levodopa.
Iloprost The risk or severity of hypotension and orthostatic hypotension can be increased when Iloprost is combined with Levodopa.
Nifedipine The risk or severity of hypotension and orthostatic hypotension can be increased when Nifedipine is combined with Levodopa.
Amiodarone The risk or severity of hypotension and orthostatic hypotension can be increased when Amiodarone is combined with Levodopa.
Diazoxide The risk or severity of hypotension and orthostatic hypotension can be increased when Diazoxide is combined with Levodopa.
Carvedilol The risk or severity of hypotension and orthostatic hypotension can be increased when Carvedilol is combined with Levodopa.

Target Protein

D(1A) dopamine receptor DRD1
D(1B) dopamine receptor DRD5
D(2) dopamine receptor DRD2
D(3) dopamine receptor DRD3
D(4) dopamine receptor DRD4

Referensi & Sumber

Synthesis reference: Vincenzo Cannata, Giancarlo Tamerlani, Mauro Morotti, "Process for the synthesis of the levodopa." U.S. Patent US4962223, issued December, 1986.
Artikel (PubMed)
  • PMID: 28012951
    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.
  • PMID: 23683503
    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.
  • PMID: 22605980
    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.
  • PMID: 2775615
    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.
  • PMID: 5171067
    Abrams WB, Coutinho CB, Leon AS, Spiegel HE: Absorption and metabolism of levodopa. JAMA. 1971 Dec 27;218(13):1912-4.
  • PMID: 20225277
    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.
Attachment

Contoh Produk & Brand

Produk: 489 • International brands: 5
Produk
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  • Apo-levocarb
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  • Apo-levocarb
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Menampilkan 8 dari 489 produk.
International Brands
  • Bidopal — GlaxoSmithKline
  • Dopar
  • Doparl — Kyowa Hakko Kirin
  • Dopasol — Daiichi Sankyo
  • Dopaston — Ohara Yakuhin

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