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Details

Stereochemistry ABSOLUTE
Molecular Formula C9H12NO7P
Molecular Weight 277.1682
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FOSLEVODOPA

SMILES

c1cc(c(cc1C[C@@]([H])(C(=O)O)N)O)OP(=O)(O)O

InChI

InChIKey=YNDMEEULGSTYJT-LURJTMIESA-N
InChI=1S/C9H12NO7P/c10-6(9(12)13)3-5-1-2-8(7(11)4-5)17-18(14,15)16/h1-2,4,6,11H,3,10H2,(H,12,13)(H2,14,15,16)/t6-/m0/s1

HIDE SMILES / InChI

Molecular Formula C9H12NO7P
Molecular Weight 277.1682
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23948989 http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021485s20lbl.pdf

Levodopa (L-DOPA) was first isolated from seedlings of Vicia faba by Marcus Guggenheim in 1913. Levodopa, a dopamine precursor, is an effective and well-tolerated dopamine replacement agent used to treat Parkinson's disease. Oral levodopa has been widely used for over 40 years, often in combination with a dopa-decarboxylase inhibitor carbidopa, which reduces many treatment complications, extending its half-life and increasing levodopa availability to the brain. Entacapone, a catechol-O-methyltransferase inhibitor, can also be used to improve the bioavailability of levodopa, especially when used in conjunction with a carbidopa.

Originator

Curator's Comment:: # Hoffmann-La Roche

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Stalevo

Approved Use

Stalevo® (carbidopa, levodopa and entacapone) is indicated to treat patients with idiopathic Parkinson’s disease.

Launch Date

1.0552032E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.946 μg/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered: CARBIDOPA, DL-
LEVODOPA plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
84.8 μg × min/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered: CARBIDOPA, DL-
LEVODOPA plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
78.7 min
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered: CARBIDOPA, DL-
LEVODOPA plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
80%
LEVODOPA plasma
Homo sapiens
Doses

Doses

DosePopulationAdverse events​
3 g 1 times / day multiple, oral
Dose: 3 g, 1 times / day
Route: oral
Route: multiple
Dose: 3 g, 1 times / day
Sources:
unhealthy, 54 years
n = 1
Health Status: unhealthy
Condition: idiopathic Parkinson's disease
Age Group: 54 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Alopecia...
AEs leading to
discontinuation/dose reduction:
Alopecia (1 patient)
Sources:
420 mg 1 times / day multiple, respiratory
Recommended
Dose: 420 mg, 1 times / day
Route: respiratory
Route: multiple
Dose: 420 mg, 1 times / day
Sources:
unhealthy, adult
84 mg 2 times / day multiple, respiratory
Recommended
Dose: 84 mg, 2 times / day
Route: respiratory
Route: multiple
Dose: 84 mg, 2 times / day
Sources:
unhealthy, adult
n = 114
Health Status: unhealthy
Condition: Parkinson’s disease
Age Group: adult
Population Size: 114
Sources:
Disc. AE: Cough...
AEs leading to
discontinuation/dose reduction:
Cough (2%)
Sources:
0.51 mg/kg 3 times / day steady, oral
Dose: 0.51 mg/kg, 3 times / day
Route: oral
Route: steady
Dose: 0.51 mg/kg, 3 times / day
Sources:
unhealthy, child|adult
n = 15
Health Status: unhealthy
Condition: Vision Impairment
Age Group: child|adult
Population Size: 15
Sources:
Other AEs: Headache, Nausea...
Other AEs:
Headache (below serious, 2 patients)
Nausea (below serious, 2 patients)
Sources:
0.76 mg/kg 3 times / day steady, oral
Dose: 0.76 mg/kg, 3 times / day
Route: oral
Route: steady
Dose: 0.76 mg/kg, 3 times / day
Sources:
unhealthy, child|adult
n = 15
Health Status: unhealthy
Condition: Vision Impairment
Age Group: child|adult
Population Size: 15
Sources:
Other AEs: Headache, Dry mouth...
Other AEs:
Headache (below serious, 1 patient)
Dry mouth (below serious, 2 patients)
Nausea (below serious, 1 patient)
Fatigue (below serious, 2 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Alopecia 1 patient
Disc. AE
3 g 1 times / day multiple, oral
Dose: 3 g, 1 times / day
Route: oral
Route: multiple
Dose: 3 g, 1 times / day
Sources:
unhealthy, 54 years
n = 1
Health Status: unhealthy
Condition: idiopathic Parkinson's disease
Age Group: 54 years
Sex: F
Population Size: 1
Sources:
Cough 2%
Disc. AE
84 mg 2 times / day multiple, respiratory
Recommended
Dose: 84 mg, 2 times / day
Route: respiratory
Route: multiple
Dose: 84 mg, 2 times / day
Sources:
unhealthy, adult
n = 114
Health Status: unhealthy
Condition: Parkinson’s disease
Age Group: adult
Population Size: 114
Sources:
Headache below serious, 2 patients
0.51 mg/kg 3 times / day steady, oral
Dose: 0.51 mg/kg, 3 times / day
Route: oral
Route: steady
Dose: 0.51 mg/kg, 3 times / day
Sources:
unhealthy, child|adult
n = 15
Health Status: unhealthy
Condition: Vision Impairment
Age Group: child|adult
Population Size: 15
Sources:
Nausea below serious, 2 patients
0.51 mg/kg 3 times / day steady, oral
Dose: 0.51 mg/kg, 3 times / day
Route: oral
Route: steady
Dose: 0.51 mg/kg, 3 times / day
Sources:
unhealthy, child|adult
n = 15
Health Status: unhealthy
Condition: Vision Impairment
Age Group: child|adult
Population Size: 15
Sources:
Headache below serious, 1 patient
0.76 mg/kg 3 times / day steady, oral
Dose: 0.76 mg/kg, 3 times / day
Route: oral
Route: steady
Dose: 0.76 mg/kg, 3 times / day
Sources:
unhealthy, child|adult
n = 15
Health Status: unhealthy
Condition: Vision Impairment
Age Group: child|adult
Population Size: 15
Sources:
Nausea below serious, 1 patient
0.76 mg/kg 3 times / day steady, oral
Dose: 0.76 mg/kg, 3 times / day
Route: oral
Route: steady
Dose: 0.76 mg/kg, 3 times / day
Sources:
unhealthy, child|adult
n = 15
Health Status: unhealthy
Condition: Vision Impairment
Age Group: child|adult
Population Size: 15
Sources:
Dry mouth below serious, 2 patients
0.76 mg/kg 3 times / day steady, oral
Dose: 0.76 mg/kg, 3 times / day
Route: oral
Route: steady
Dose: 0.76 mg/kg, 3 times / day
Sources:
unhealthy, child|adult
n = 15
Health Status: unhealthy
Condition: Vision Impairment
Age Group: child|adult
Population Size: 15
Sources:
Fatigue below serious, 2 patients
0.76 mg/kg 3 times / day steady, oral
Dose: 0.76 mg/kg, 3 times / day
Route: oral
Route: steady
Dose: 0.76 mg/kg, 3 times / day
Sources:
unhealthy, child|adult
n = 15
Health Status: unhealthy
Condition: Vision Impairment
Age Group: child|adult
Population Size: 15
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Levodopa-induced postural hypotension. Treatment with fludrocortisone.
1975 Jan
[Abnormal movements induced by L-dopa. New therapeutic possibilities].
1975 Jan 25
Reduction of dyskinesia and induction of akinesia induced by morphine in two parkinsonian patients with severe sciatica.
1999
A unified dyskinesias rating scale for L-dopa-induced dyskinesias?
1999
Levodopa-induced dyskinesias treated by pallidotomy.
1999 Aug 1
Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation.
1999 Aug 11
Comparison of pallidal and subthalamic nucleus deep brain stimulation for advanced Parkinson's disease: results of a randomized, blinded pilot study.
1999 Dec
Drug-induced motor complications in dopa-responsive dystonia: implications for the pathogenesis of dyskinesias and motor fluctuations.
1999 Jul-Aug
Internal globus pallidus discharge is nearly suppressed during levodopa-induced dyskinesias.
1999 Nov
Dopamine D2 receptor gene polymorphism and the risk of levodopa-induced dyskinesias in PD.
1999 Oct 22
Functional mapping of the human globus pallidus: contrasting effect of stimulation in the internal and external pallidum in Parkinson's disease.
2000
Tolcapone increases maximum concentration of levodopa.
2000
Preventing levodopa-induced dyskinesias.
2000 Apr
Investigating levodopa-induced dyskinesias in the parkinsonian primate.
2000 Apr
Sleep attacks and Parkinson's disease treatment.
2000 Apr 15
[Dopaminergic agonists in the treatment of Parkinson's disease].
2000 Dec
Evidence of functional somatotopy in GPi from results of pallidotomy.
2000 Dec
Effect of subthalamic nucleus stimulation on levodopa-induced dyskinesia in Parkinson's disease.
2000 Dec 26
Embryonic ventral mesencephalic grafts improve levodopa-induced dyskinesia in a rat model of Parkinson's disease.
2000 Jul
Population pharmacokinetics of levodopa in patients with Parkinson's disease treated with tolcapone.
2000 Jun
[Worsened orthostatic hypotension due to levodopa administration in a case of Parkinson's disease].
2000 Mar
Levodopa-induced dyskinesias in autopsy-proven cortical-basal ganglionic degeneration.
2000 Mar
The effect of amantadine on levodopa-induced dyskinesias in Parkinson's disease: a double-blind, placebo-controlled study.
2000 Mar-Apr
Levodopa-induced dyskinesias in Parkinson's disease: is sensitization reversible?
2000 May
Detection and assessment of the severity of levodopa-induced dyskinesia in patients with Parkinson's disease by neural networks.
2000 Nov
Centrally initiated postural adjustments in parkinsonian patients on and off levodopa.
2000 Nov
Workshop IV: drug treatment guidelines for the long-term management of Parkinson's disease.
2000 Sep
Beneficial effects of amantadine on L-dopa-induced dyskinesias in Parkinson's disease.
2000 Sep
Adverse drug reactions to selegiline: a review of the French pharmacovigilance database.
2000 Sep-Oct
Pharmacokinetic-pharmacodynamic relationship of levodopa with and without tolcapone in patients with Parkinson's disease.
2001
Melanogenesis by tyrosinase action on 3,4-dihydroxyphenylalanine (DOPA) in the presence of polyethylene glycol: a matrix-assisted laser desorption/ionization mass spectrometric investigation.
2001
A study of excessive daytime sleepiness and its clinical significance in three groups of Parkinson's disease patients taking pramipexole, cabergoline and levodopa mono and combination therapy.
2001
Efficacy and tolerability of entacapone as adjunctive therapy to levodopa in patients with Parkinson's disease and end-of-dose deterioration in daily medical practice: an open, multicenter study.
2001
Dimeric L-dopa derivatives as potential prodrugs.
2001 Apr 23
SCH 58261, an A(2A) adenosine receptor antagonist, counteracts parkinsonian-like muscle rigidity in rats.
2001 Aug
Dopamine D(2) receptors regulate tyrosine hydroxylase activity and phosphorylation at Ser40 in rat striatum.
2001 Feb
Induction by dopamine D1 receptor agonist ABT-431 of dyskinesia similar to levodopa in patients with Parkinson disease.
2001 Feb
Molecular mechanisms controlling the rate and specificity of catechol O-methylation by human soluble catechol O-methyltransferase.
2001 Feb
Accelerometric assessment of levodopa-induced dyskinesias in Parkinson's disease.
2001 Jan
SPECT imaging of the dopamine transporter in juvenile-onset dystonia.
2001 Jan 23
Enhanced abilities of highly swollen chitosan beads for color removal and tyrosinase immobilization.
2001 Jan 29
Biogenic aldehyde(s) derived from the action of monoamine oxidase may mediate the antidipsotropic effect of daidzin.
2001 Jan 30
Role of peroxynitrite in macrophage microbicidal mechanisms in vivo revealed by protein nitration and hydroxylation.
2001 Jun 1
Resveratrol and a novel tyrosinase in Carignan grape juice.
2001 Mar
Effects of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on alpha2-adrenoceptors which regulate the synthesis and release of noradrenaline in the rat brain.
2001 Mar
Event-related functional magnetic resonance imaging in Parkinson's disease before and after levodopa.
2001 Mar
Levodopa-induced drowsiness in healthy volunteers: results of a choice reaction time test combined with a subjective evaluation of sedation.
2001 Mar-Apr
Parkinsonism after glycine-derivate exposure.
2001 May
Speech dysfluency exacerbated by levodopa in Parkinson's disease.
2001 May
Chromium(VI) reduction by catechol(amine)s results in DNA cleavage in vitro: relevance to chromium genotoxicity.
2001 May
Patents

Sample Use Guides

Maximum dosage in a 24-hour period is eight tablets (Stalevo 50, containing 12.5 mg of carbidopa, 50 mg of levodopa and 200 mg of entacapone; Stalevo 75, containing 18.75 mg of carbidopa, 75 mg of levodopa and 200 mg of entacapone; Stalevo 100, containing 25 mg of carbidopa, 100 mg of levodopa and 200 mg of entacapone; Stalevo 125, containing 31.25 mg of carbidopa, 125 mg of levodopa and 200 mg of entacapone; Stalevo 150, containing 37.5 mg of carbidopa, 150 mg of levodopa and 200 mg of entacapone; Stalevo 200, containing 50 mg of carbidopa, 200 mg of levodopa and 200 mg of entacapone). The optimum daily dosage must be determined by careful titration in each patient.
Route of Administration: Oral
Low dose (<30 uM) Levodopa protects PC12 cells against oxidative stress which might be related to the up-regulation of CD39 and pCREB expression.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:43:29 UTC 2021
Edited
by admin
on Fri Jun 25 21:43:29 UTC 2021
Record UNII
37NQZ0J76I
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FOSLEVODOPA
INN   USAN  
Official Name English
FOSLEVODOPA [USAN]
Common Name English
3-HYDROXY-O-PHOSPHONO-L-TYROSINE
Common Name English
L-TYROSINE, 3-HYDROXY-O-PHOSPHONO-
Common Name English
ABBV-951 COMPONENT FOSLEVODOPA
Code English
L-TYROSINE, 3-HYDROXY-, 4-(DIHYDROGEN PHOSPHATE)
Systematic Name English
FOSLEVODOPA [INN]
Common Name English
LEVODOPA-4'-MONOPHOSPHATE
Common Name English
Code System Code Type Description
CAS
97321-87-4
Created by admin on Fri Jun 25 21:43:29 UTC 2021 , Edited by admin on Fri Jun 25 21:43:29 UTC 2021
PRIMARY
FDA UNII
37NQZ0J76I
Created by admin on Fri Jun 25 21:43:29 UTC 2021 , Edited by admin on Fri Jun 25 21:43:29 UTC 2021
PRIMARY
INN
11006
Created by admin on Fri Jun 25 21:43:29 UTC 2021 , Edited by admin on Fri Jun 25 21:43:29 UTC 2021
PRIMARY
PUBCHEM
127766
Created by admin on Fri Jun 25 21:43:29 UTC 2021 , Edited by admin on Fri Jun 25 21:43:29 UTC 2021
PRIMARY
NCI_THESAURUS
C166651
Created by admin on Fri Jun 25 21:43:29 UTC 2021 , Edited by admin on Fri Jun 25 21:43:29 UTC 2021
PRIMARY
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