DOPA

197.18800

197.19

200-445-2

46627O600J

759573|118381

DTXSID9023209

C611

Colorless to white crystals or crystalline powder; needles from water

N04BA01|N04BA03|N04BA02|N - Nervous system

2932999099

103.78000

0.75250

Solid

1.51 g/cm³

284-286 °C

448.4±45.0 °C at 760 mmHg

225.0±28.7 °C

-12 ° (C=5, 1mol/L HCl)

Slightly soluble in water, dilute hydrochloric acid and formic acid. Insoluble in ethanol.

2-8°C

LD50 in mice (mg/kg): 3650 ±327 orally, 1140 ±66 i.p., 450 ±42 i.v., >400 s.c.; in male, female rats (mg/kg): >3000, >3000 orally; 624, 663 i.p.; >1500, >1500 s.c. (Clark)

Specific optical rotation: -13.1 deg @ 13 °C/D (c= 5.12 in 1 N HCl); max absorption (0.001 N HCl): 220.5 nm (log e= 3.79); 280 nm (log e= 3.42)

Odorless

Tasteless

pKa = 2.32

148.7 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]|138.21 Ų [M-H]- [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]|144.27 Ų [M-H]- [CCS Type: DT, Method: stepped-field]|149.4 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]|147.5 Ų [M+Na]+ [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]|140.6 Ų [M-H]- [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]|141.2 Ų [M+Na-2H]- [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]|145.4 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]|141.6 Ų [M-2H+Na]-

NONH for all modes of transport

3

R22; R36/37/38; R20/21/22

S26; S36; S24/25

AY5600000

Xn

Stable. Incompatible with strong oxidizing agents. Light and air sensitive.

P301 + P312 + P330-P305 + P351 + P338

H302-H315-H319-H335

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl levodopa, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

REVIEW WITH 65 REF ON ROLE OF ENDOGENOUS AMINES IN TREATMENT OF PARKINSON'S WITH L-DOPA.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P261, P264, P270, P271, P273, P280, P281, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P330, P332+P313, P337+P313, P362, P391, P403+P233, P405, and P501|Aggregated GHS information provided by 187 companies from 20 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

There is no readily available data for the use of levodopa in pregnancy. Rabbits treated with levodopa and carbidopa produced smaller litters and their offspring developed visceral and skeletal deformities. Levodopa may lower prolactin and interfere with lactation but there is limited human data to demonstrate this effect. 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 mothers. There is currently a lack of data on the safety and effectiveness of using levodopa in pediatric patients. 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 treatment.|IDENTIFICATION: Levodopa is used as a drug for treating Parkinsons disease. Levodopa is white or almost white crystalline powder, which darkens on exposure to air and light. Levodopa is odourless and almost tasteless. It is slightly soluble in water. Soluble in aqueous solutions of mineral acids and alkali carbonates; practically insoluble in alcohol, chloroform, and ether. HUMAN EXPOSURE: Main risks and target organs: The principal target organ is Central Nervous System. The main risks are cardiovascular. Additional risks are associated with the gastrointestinal tract, and the peripheral as well as the central nervous system. Summary of clinical effects: Nausea and anorexia commonly occur and may be accompanied by vomiting. Another effect includes abdominal pain, constipation, diarrhea and dysphagia; dyspepsia and gastrointestinal bleeding. The commonest cardiovascular effect is postural hypotension, with faintness and dizziness. There may be palpitations often accompanied by excess sweating. Cardiac arrhythmias, particularly atrial and ventricular ectopic beats, have been reported and hypertension has occasionally occurred. Psychiatric symptoms include agitation, anxiety, elation and insomnia or some times drowsiness and depression. More severe effects include aggression, paranoid delusions, hallucinations, suicidal behaviour and unmasking of dementia. Involuntary movements are very common and usually start in the mouth, jaws or tongue. Abnormal limb movements often develop after several months and severe choreoathetoid movements may also occur after prolonged high doses. Oculogyric movements may rarely be exacerbated and muscle twitching and blepharospasm occur occasionally. Headache, weakness, ataxia, and rarely paraesthesia and convulsions have occurred. Polyuria, incontinence, and difficulty in micturition may occur. Blurred vision, mydriasis, diplopia and glaucoma are rare. Uncommon effects include transient rises in tests for liver function and blood urea nitrogen, abnormal respiratory movements, loss of hair, skin rashes, activation of Horner's syndrome, weight changes, and rarely agranulocytosis or hemolytic anemia. Administration without benserazide: The dose producing maximal improvement with tolerated side effect must be determined and carefully titrated for each individual patient. Contraindications: Levodopa is contraindicated for melanoma and glaucoma in patients with known hypersensitivity to the drug. Levodopa should be administered cautiously to patients with severe cardiovascular or pulmonary disease, asthma, renal, hepatic or endocrine disease. Care should be exercised in administering levodopa to patients with history of myocardial infarction who have residual atrial nodal or ventricular arrhythmias. If levodopa is necessary in this type of patient, it should be used in a facility with a coronary care unit or an intensive care unit. One must be on the alert for the possibility of upper gastrointestinal hemorrhage in those patients with a past history of peptic ulcer disease. Levodopa is contraindicated in patients with severe psychotic disorders, it should be used with caution in patients with psychiatric disturbance. This drug should not be used in pregnancy and should not be used in nursing mothers. The safety under the age of 12 has not been established. Routes of entry: Oral: The route of entry of levodopa is oral. Absorption by route of exposure: Levodopa is rapidly absorbed from the small intestine by an active transport system for aromatic amino acids. Concentrations of drug in plasma usually peak between 0.5 and 2 hours after an oral dose. The rate of absorption of levodopa is greatly dependent upon the rate of gastric emptying, the pH of gastric juice and the length of time the drug is exposed to the degradative enzymes of the gastric mucosa and intestinal flora. Hyperacidity of gastric juice, and competition for absorption sites in the small intestine by amino acids each may interfere with the bioavailability of vodopa. Distribution by route of exposure: It is widely distributed to most body tissues, but less to the central nervous system (CNS). Little unchanged drug reaches the cerebral circulation and probably less than 1% penetrates into the CNS. Biological half-life by route of exposure: Levodopa has relatively short plasma half-life of 1 to 3 hours. Metabolism: More than 95% of levodopa is decarboxylated by the widely distributed extracerebral aromatic l-amino acid decarboxylase. The drug is extensively decarboxylated in its first passage through the liver, which is rich in decarboxylase. A small amount is methylated to 3-0-methyldopa, which accumulates in the CNS due to its long half-life. Most is converted to dopamine, small amounts of which in turn are metabolized to norepinephrine and epinephrine (adrenaline). Biotransformation of dopamine proceeds rapidly to yield the principal excretion products, 3-4-dihydroxy-phenylacetic acid (DOPAC) and 3-methoxy-4-hydroxy-phenylacetic acid (homovanillic acid, HVA). At least 30 metabolites of levodopa have been identified. The evidence indicates that the metabolism of levodopa may be accelerated during prolonged therapy possibly due to enzyme induction. Elimination by route of exposure: Oral: Excretion: Metabolites of dopamine are rapidly excreted in the urine; 80% of a radioactively labelled dose is recovered within 24 hours. The principal metabolites DOPAC and HVA account for up to 50% of the administered dose. Negligible amounts are found in the feces. Mode of action: Toxicodynamics: Peripheral decarboxylation of levodopa markedly increases the concentration of dopamine in blood. Dopamine is a pharmacologically active catecholamine with prominent effects of alpha and beta adrenergic receptors, and this point give the potentially toxic effects. Pharmacodynamics: Levodopa is the metabolic precursor of dopamine, does cross the blood-brain barrier, and presumably is converted to dopamine in the basal ganglia. This is thought to be the mechanism whereby levodopa relieves symptoms of Parkinson's disease, because it replaces depleted brain dopamine in these patients. Interactions: Doses of pyridoxine that are only modestly in excess of the recommended dietary allowance enhance the extracerebral metabolism of levodopa at this step. Antipsychotic drugs, such as phenothiazines, butyrophenones and reserpine can produce a parkinsonism-like syndrome, and since these drugs interfere with the therapeutic effects of levodopa, they are contraindicated. Therefore the phenothiazines should not be used to combat the emetic effect of levodopa. Nonspecific monoamine oxidase inhibitors interfere with inactivation of dopamine, norepinephrine and other catecholamines. Hence, they unpredictably exaggerate the central effects of levodopa and its catecholamine metabolites. Hypertensive crisis and hyperpyrexia are very real and dangerous sequelae of concurrent administration of two such drugs. Anticholinergic drugs such as phenidyl, benztropine, procyclidine and others act synergistically with levodopa to improve certain symptoms of parkinsonism, especially tremor. However, large doses of anticholinergic drugs can slow gastric emptying sufficiently to cause a delay in reabsorption of levodopa by the small intestine. The effect of levodopa is enhanced by amantadine, benserazide, carbidopa, atropine and amphetamine. Concurrent administration of levodopa with guanethidine, methyldopa and other antihypertensive agents may cause increased hypotension. Cardiac arrhythmias due to levodopa may be augmented by anaesthetic agents, such as cyclopropane or halothane. Sympathomimetic agents such as epinephrine (adrenaline) or isoprenaline may also enhance the cardiac side effects of levodopa. Beta-adrenergic blocking agents such as propranolol may enhance the action of levodopa on tremor and diminish the cardiac side effects. In some patient the administration of antacids with levodopa may enhance the gastrointestinal absorption of levodopa. Main adverse effects: Rarely, oculogyric crises, sense of stimulation, hiccups, edema, loss of hair hoarseness, priapism and activation of latent Horner's syndrome have been observed. Elevation of blood urea nitrogen, SGOT, SGPT, LDH, bilirubin, alkaline phosphatase or protein-bound iodine have been reported, occasional reduction in WBC, hemoglobin and haematocrit have been noted. Leucopenia has occurred and requires cessation at least temporarily, of levodopa administration. Acute poisoning: Ingestion: Spasm or closing of eyelids are possible early sign of overdose. Nausea, vomiting, cardiac arrhythmias, involuntary movements of the body, including the face, tongue, arms, hand, head, and upper body; choreiform and other involuntary movements occur in 50% to 80% of patients. This effect is dose related. Psychiatric disturbances are usually present. Hypotension, hemolytic anemia, urinary retention, duodenal ulcer, sialorrhea, ataxia, abdominal pain, dry mouth, nightmares, tachypnea, bruxism, confusion, insomnia also occur. Special risks: Pregnancy, breast-feeding: Levodopa represent a risk for pregnancy and the nursing mother. Use of medication should be carefully considered in conjunction with bronchial asthma, emphysema and other severe pulmonary cardiovascular disease; history of convulsive disorders, diabetes, endocrine diseases, glaucoma, hepatic function impairment, history of suspected melanoma, history of myocardial infarction with residual history of peptic ulcer, psychotic states, renal function impairment, urinary retention. ANIMAL/PLANT STUDIES: Teratogenicity: Studies in rabbits have shown that levodopa causes visceral and skeletal malformations in offspring.

The combination of levodopa and carbidopa has been reported to cause serum aminotransferase elevations in up to 9% of patients, but these abnormalities are usually mild, asymptomatic and self-limiting. In rare instances, the aminotransferase elevations rise above 5 to 10 times the ULN and require discontinuation or dose adjustment. In addition, levodopa has been implicated in a small number of cases of clinically apparent, acute liver injury, but the clinical characteristics and typical pattern of enzyme elevations have not been characterized. There have been no published case reports of clinically apparent liver injury convincingly attributed to levodopa. In view of the long term and wide scale use of levodopa in Parkinson disease, clinically apparent liver injury with jaundice must be exceedingly rare.

The pharmacokinetics of levodopa (LD) with & without pramipexole in men & postmenopausal women with Parkinson's disease /were studied/. Patients on stable dose of carbidopa/LD were randomized to receive escalating doses of placebo or pramipexole over 7 wks. LD & pramipexole pharmacokinetics were performed after a single test dose 25/100 of carbidopa/LD, before initiation of pramipexole or placebo, at 1.5 mg/d & 4.5 mg/d of pramipexole or placebo. Compared to men, women had greater LD bioavailability. Pramipexole did not alter LD bioavailability, & pramipexole pharmacokinetics were equivalent in men & women.|Admin of levodopa with nonspecific inhibitors of MAO, such as phenelzine & tranylcypromine, markedly accentuates the actions of levodopa & may precipitate life-threatening hypertensive crisis & hyperpyrexia; nonspecific MAO inhibitors always should be discontinued at least 14 days before levodopa is admin (note that this prohibition does not include the MAO-B subtype-specific inhibitor selegiline, which, as discussed below, often is admin safely in combination with levodopa). Abrupt withdrawal of levodopa or other dopaminergic medications may precipitate the neuroleptic malignant syndrome more commonly observed after treatment with dopamine antagonists.|Conventional antipsychotic agents, such as the phenothiazines, ... may cause marked worsening of parkinsonism, probably through actions at the D2 dopamine receptor.|TRICYCLIC ANTIDEPRESSANTS...GIVEN CONCOMITANTLY WITH LEVODOPA EVOKE HYPERTENSIVE CRISES.|For more Interactions (Complete) data for LEVODOPA (33 total), please visit the HSDB record page.

LD50 Rat oral 1780 mg/kg|LD50 Rat ip 624 mg/kg|LD50 Mouse oral 2363 mg/kg|LD50 Mouse ip 588 mg/kg|For more Non-Human Toxicity Values (Complete) data for LEVODOPA (7 total), please visit the HSDB record page.

Levodopa binding to plasma proteins is negligible.

/L-DOPA/ IS NATURALLY OCCURRING FORM OF DOPA...THE BIOLOGICAL PRECURSOR OF CATECHOLAMINES.

...DRUG...MAY APPEAR IN MILK.

... Mean plasma levodopa concn ranged between 0.45-7.07 ug/ml & peak concns between 0.95-13.75 ug/ml. In 44 of 58 dosing events, an oral dose of levodopa was related to a peak in plasma concn. ...

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. Levodopa is most commonly formulated as an oral tablet with a peripheral dopa decarboxylase inhibitor indicated for treatment of Parkinson's disease, post-encephalitic parkinsonism, and symptomatic parkinsonism following carbon monoxide intoxication or manganese intoxication.|FDA Label|Inbrija is indicated for the intermittent treatment of episodic motor fluctuations (OFF episodes) in adult patients with Parkinson's disease (PD) treated with a levodopa/dopa-decarboxylase inhibitor.|Levodopa/Carbidopa/Entacapone Orion is indicated for the treatment of adult patients with Parkinson's disease and end-of-dose motor fluctuations not stabilised on levodopa / dopa-decarboxylase (DDC)-inhibitor treatment.|Stalevo is indicated for the treatment of adult patients with Parkinson's disease and end-of-dose motor fluctuations not stabilised on levodopa / dopa-decarboxylase (DDC)-inhibitor treatment.|Corbilta is indicated for the treatment of adult patients with Parkinson's disease and end-of-dose motor fluctuations not stabilised on levodopa/dopa decarboxylase (DDC) inhibitor treatment.,|Symptomatic treatment of adult patients with Parkinson's disease|Treatment of Parkinson's disease

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. 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.

Parkinson Disease Agents

Levodopa is indicated to alleviate symptoms and allow more normal body movements with improved muscle control in the treatment of idiopathic Parkinson's disease, postencephalitic parkinsonism, or symptomatic parkinsonism that may follow injury to the nervous system by carbon monoxide intoxication or manganese intoxication. It is also indicated in parkinsonism associated with cerebral arteriosclerosis. /Included in US product labeling/|Levodopa, the metabolic precursor of dopamine, is the single most effective agent in the treatment of Parkinson's Disease.|LEVODOPA AFFORDS ONLY SYMPTOMATIC RELIEF OF PARKINSONISM. IF DRUG IS STOPPED, ALL PREEXISTING SYMPTOMS GRADUALLY RETURN WITHIN WK OR TWO; UPON RESUMPTION OF L-DOPA THERAPY AFTER PERIOD OF WITHDRAWAL, PREVIOUS THERAPEUTIC RESPONSE IS REESTABLISHED AFTER WK OR MORE.|...L-DOPA...HAS BEEN MORE CONSISTENTLY EFFECTIVE IN TREATMENT OF CHRONIC MANGANESE POISONING THAN IN PARKINSON'S DISEASE.|For more Therapeutic Uses (Complete) data for LEVODOPA (17 total), please visit the HSDB record page.

PT WITH CARDIAC ARRHYTHMIAS OR HISTORY OF MYOCARDIAL INFARCTION SHOULD UNDERGO INITIAL THERAPY WITH LEVODOPA ONLY IN FACILITY EQUIPPED FOR INTENSIVE CORONARY CARE. ...DIABETIC PT...SHOULD BE CAREFULLY MONITORED FOR ANY NECESSITY TO MODIFY THEIR REGIMEN. CAUTION ALSO NECESSARY IN PT WITH HISTORY OF PEPTIC ULCER, CONVULSIONS...|DISCONTINUATION OF LEVODOPA THERAPY FOR 6-24 HR PRIOR TO GENERAL ANESTHESIA IS RECOMMENDED... SAFETY OF L-DOPA DURING PREGNANCY HAS NOT BEEN ESTABLISHED, HOWEVER, INFANTS SHOULD NOT BE NURSED BY MOTHERS RECEIVING DRUG SINCE IT MAY APPEAR IN MILK. ...DRUG MAY INHIBIT LACTATION.|...IS CONTRAINDICATED IN PATIENTS WITH NARROW-ANGLE GLAUCOMA, ACUTE PSYCHOSIS, OR SEVERE PSYCHONEUROSIS. IT SHOULD NOT BE ADMIN TO PT WITH UNCOMPENSATED ENDOCRINE, RENAL, HEPATIC, CARDIOVASCULAR, OR PULMONARY DISEASE. /USE/...EXTREME CAUTION IN PT WITH ASTHMA OR EMPHYSEMA WHO MAY REQUIRE SYMPATHOMIMETIC DRUGS.|SINCE LEVODOPA THERAPY...ASSOC WITH INCR GROWTH OF MELANOMA, PT WITH KNOWN MELANOMAS OR PIGMENTED LESIONS SHOULD BE CAREFULLY MONITORED FOR CHANGES IN SUCH LESIONS & DRUG WITHDRAWN IF CHANGES OCCUR.|For more Drug Warnings (Complete) data for LEVODOPA (49 total), please visit the HSDB record page.

Levodopa therapy can have a dramatic effect on all the signs & symptoms of /Parkinson's Disease/. Early in the course of the disease, the degree of improvement in tremor, rigidity, & bradykinesia may be nearly complete. In early PD, the duration of the beneficial effects of levodopa may exceed the plasma lifetime of the drug, suggesting that the nigrostriatal dopamine system retains some capacity to store & release dopamine. A principal limitation of the long-term use of levodopa therapy is that, with time, this apparent "buffering" capacity is lost, & the patient's motor state may fluctuate dramatically with each dose of levodopa. A common problem is the development of the "wearing off" phenomenon; each dose of levodopa effectively improves mobility for a period of time, perhaps 1-2 hr, but rigidity & akinesia rapidly return at the end of the dosing interval. Increasing the dose & frequency of admin can improve this situation, but this often is limited by development of dyskinesias, excessive & abnormal involuntary movements. Dyskinesias are observed most often when the plasma levodopa concn is high, although, in some individuals, dyskinesias or dystonia may be triggered when the level is rising or falling. These movements can be as uncomfortable & disabling as the rigidity & akinesia of PD. In the later stages of PD, patients may fluctuate rapidly between being "off," having no beneficial effects from their medications, & being "on" but with disabling dyskinesias, a situation called to "on/off phenomenon."

Levodopa is able to cross the blood-brain barrier while dopamine is not. The addition of a peripheral dopa decarboxylase inhibitor prevents the conversion of levodopa to dopamine in the periphery so that more levodopa can reach the blood-brain barrier. Once past the blood-brain barrier, levodopa is converted to dopamine by aromatic-L-amino-acid decarboxylase.

Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons. (See all compounds classified as Dopamine Agents.)|Agents used in the treatment of Parkinson's disease. The most commonly used drugs act on the dopaminergic system in the striatum and basal ganglia or are centrally acting muscarinic antagonists. (See all compounds classified as Antiparkinson Agents.)

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.|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|168L for orally inhaled levodopa.|Intravenously administered levodopa is cleared at a rate of 14.2mL/min/kg in elderly patients and 23.4mL/min/kg in younger patients. When given carbidopa, the clearance of levodopa was 5.8mL/min/kg in elderyly patients and 9.3mL/min/kg in younger patients.|...DRUG...MAY APPEAR IN MILK.|AFTER IP INJECTION INTO MICE, BIOTRANSFORMATION OF 60% OF RADIOACTIVELY LABELLED DL-DOPA TAKES PLACE WITHIN 10 MIN, & PEAK DOPAMINE LEVELS ARE REACHED 20 MIN AFTER ADMIN. ...APPROX 0.1% OF DOSE WAS PRESENT IN THE BRAIN AS (14)C-L-DOPA OR (14)C-DOPAMINE. /DL-DOPA/|MORE THAN 95% OF LEVODOPA IS DECARBOXYLATED IN PERIPHERY BY WIDELY DISTRIBUTED EXTRACEREBRAL AROMATIC L-AMINO ACID DECARBOXYLASE. ...LITTLE UNCHANGED DRUG REACHES CEREBRAL CIRCULATION & PROBABLY LESS THAN 1% PENETRATES INTO CNS.|MOST IS CONVERTED TO DOPAMINE... DOPAMINE METABOLITES ARE RAPIDLY EXCRETED IN URINE, ABOUT 80% OF RADIOACTIVELY LABELED DOSE BEING RECOVERED WITHIN 24 HR. ... THESE METABOLITES /3,4-DIHYDROXYPHENYLACETIC ACID & 3-METHOXY-4-HYDROXYPHENYLACETIC ACID/, AS WELL AS SMALL AMT OF LEVODOPA & DOPAMINE, ALSO APPEAR IN CEREBROSPINAL FLUID.|For more Absorption, Distribution and Excretion (Complete) data for LEVODOPA (11 total), please visit the HSDB record page.

Levodopa is either converted to dopamine by aromatic-L-amino-acid decarboxylase or O-methylated to 3-O-methyldopa by catechol-O-methyltransferase. 3-O-methyldopa cannot be metabolized to dopamine. Once levodopa is converted to dopamine, it is converted to sulfated or glucuronidated metabolites, epinephrine E, or homovanillic acid through various metabolic processes. The primary metabolites are 3,4-dihydroxyphenylacetic acid (13-47%) and homovanillic acid (23-39%).|MOST IS CONVERTED TO DOPAMINE... BIOTRANSFORMATION OF DOPAMINE PROCEEDS RAPIDLY...EXCRETION PRODUCTS, 3,4-DIHYDROXYPHENYLACETIC ACID...& 3-METHOXY-4-HYDROXYPHENYLACETIC ACID... SOME BIOCHEMICAL EVIDENCE INDICATES THAT ACCELERATION OF LEVODOPA METABOLISM OCCURS DURING PROLONGED THERAPY, POSSIBLY DUE TO ENZYME INDUCTION.|MORE THAN 95%...IS DECARBOXYLATED...BY...AROMATIC L-AMINO ACID DECARBOXYLASE. ... A SMALL AMT /OF L-DOPA/ IS METHYLATED TO 3-O-METHYL-DOPA... MOST IS CONVERTED TO DOPAMINE, SMALL AMT OF WHICH IN TURN ARE METABOLIZED TO NOREPINEPHRINE & EPINEPHRINE.|...IS ESTIMATED THAT ABOUT THREE FOURTHS OF DIETARY METHIONINE IS UTILIZED FOR METABOLISM OF LARGE THERAPEUTIC DOSES OF LEVODOPA.|LEVODOPA (L-DOPA) IS FORMED IN MAMMALS FROM L-TYROSINE AS INTERMEDIARY METABOLITE IN ENZYMATIC SYNTHESIS OF CATECHOLAMINES.

2.3 hours for orally inhaled levodopa. 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.|THE HALF-LIFE IN PLASMA IS SHORT (1-3 HR).

Levodopa by various routes crosses the blood brain barrier, is decarboxylated to form dopamine. This supplemental dopamine performs the role that endogenous dopamine cannot due to a decrease of natural concentrations and stimulates dopaminergic receptors.|MOST WIDELY ACCEPTED THEORY IS THAT LEVODOPA INCR LEVEL OF DOPAMINE & THUS ACTIVATION OF DOPAMINE RECEPTORS IN EXTRA-PYRAMIDAL CENTERS IN THE BRAIN (PRIMARILY IN CAUDATE NUCLEUS & SUBSTANTIA NIGRA).|The present data indicate that the major effects observed after administration of exogenous levodopa are not due to a direct action of levodopa on dopamine receptors, or to extrastriatal release of dopamine, but to conversion of levodopa to dopamine by serotonergic terminals and probably some intrastriatal cells.|EFFECTS OF LEVODOPA ON HUMAN & MURINE MELANOMA CELLS EXAMINED. WHEN EXPONENTIALLY GROWING CELLS WERE EXPOSED TO L-DOPA, CHARACTERISTIC INHIBITION OF THYMIDINE INCORPORATION OBSERVED.|IN RATS, DOPAMINERGIC AGONISTS ALL CAUSED DECR IN SERUM PROLACTIN LEVELS.

/SRP:/ Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/HUMAN EXPOSURE STUDIES/ Application of levodopa to the eyes of normal people has shown that it can induce mydriasis at sufficiently high concentrations.|/CASE REPORTS/ The case of a 70-yr-old woman with a long history of Parkinson's disease taking Sinemet-275 (25 mg carbidopa, combination, 250 mg levodopa), at a maximum dose of 8 tablets/day for 13 yr, who was noted to have intense black pigmentation confined to the costal cartilages at necropsy, is reported. It was suggested that failure to metabolize high plasma levels of levodopa in the presence of a dopa-decarboxylase inhibitor had resulted in the deposition of dihydroxyphenylalanine in the costal cartilage of the patient.|/CASE REPORTS/ Acute overdose was reported in a 61-yr old man following ingestion of 100 g of levodopa. He experienced hypertension initially, followed by hypotension for a few hrs, mild nausea, & severe anorexia that gradually resolved over 1 wk. He had insomnia for about 1 wk, confusion for 2 days, & agitation for 3-4 days.

3 Hydroxy L tyrosine

CAPSULES USP: 100, 250, & 500 MG; TABLETS USP: 100, 250, & 500 MG.|Levodopa is one of the main ingredients along with carbidopa in the drug Sinemet ... (tablets)|Levodopa is one of the main ingredients along with carbidopa in the drug Atamet ... (tablets)

L-Tyrosine, 3-hydroxy-: ACTIVE

Analyte: levodopa; matrix: pharmaceutical preparation (tablet); procedure: liquid chromatography with detection at 280 nm and comparison to standards (assay purity)|Analyte: levodopa; matrix: pharmaceutical preparation (tablet); procedure: infrared absorption spectrophotometry with comparison to standards (chemical identification)|Analyte: levodopa; matrix: pharmaceutical preparation (capsule); procedure: ultraviolet absorption spectrophotometry with detection at 280 nm and comparison to standards (assay purity)|Analyte: levodopa; matrix: pharmaceutical preparation (capsule); procedure: infrared absorption spectrophotometry with comparison to standards (chemical identification)|For more Analytic Laboratory Methods (Complete) data for LEVODOPA (10 total), please visit the HSDB record page.

HPLC SYSTEM USED TO ANALYZE PLASMA & BIOLOGICAL FLUIDS CONSISTED OF A GUARD COLUMN DRY-PACKED WITH PERISORB RB-18, REVERSED-PHASE COLUMN WITH BECKMAN-ULTRASPHERE-ODS & A MOBILE PHASE WITH SODIUM ACETATE/CITRIC ACID/METHANOL (6.3:3.2:0.5).

Human drugs -> Inbrija -> EMA Drug Category|Anti-Parkinson drugs -> Human pharmacotherapeutic group|Human drugs -> Levodopa/Carbidopa/Entacapone Orion -> EMA Drug Category|Nervous sytem -> Human pharmacotherapeutic group|Human drugs -> Stalevo -> EMA Drug Category|Human drugs -> Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz) -> EMA Drug Category|Human drugs -> Numient -> EMA Drug Category|Human drugs -> Rare disease (orphan)|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals