L-DOPA
L-DOPA Uses, Dosage, Side Effects, Food Interaction and all others data.
L-DOPA is a prodrug of dopamine that is administered to patients with Parkinson's due to its ability to cross the blood-brain barrier. L-DOPA 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. 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. 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.
L-DOPA 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.
| Trade Name | L-DOPA |
| Availability | Prescription only |
| Generic | Levodopa |
| Levodopa Other Names | Dihydroxy-L-phenylalanine, L-DOPA, Levodopa, Levodopum |
| Related Drugs | Sinemet, Rytary, Gocovri, Sinemet CR, ropinirole, pramipexole, benztropine, carbidopa / levodopa, Requip, Mirapex |
| Type | |
| Formula | C9H11NO4 |
| Weight | Average: 197.1879 Monoisotopic: 197.068807845 |
| Protein binding | Levodopa binding to plasma proteins is negligible. |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
L-DOPA is a dopamine precursor used in the management of Parkinson's disease, often in combination with carbidopa, as well as other conditions associated with parkinsonism.
L-DOPA 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. L-DOPA 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.
L-DOPA is also used to associated treatment for these conditions: Paralysis agitans, Parkinson's Disease (PD), Parkinsonism, Postencephalitic parkinsonism, Restless Legs Syndrome (RLS), Advanced Motor fluctuations
How L-DOPA works
L-DOPA 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.
Toxicity
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. L-DOPA may lower prolactin and interfere with lactation but there is limited human data to demonstrate this effect. L-DOPA 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.
Food Interaction
- Avoid multivalent ions. Iron salts may reduce levodopa absorption.
- Take with or without food. A diet high in protein may delay absorption and AUC of levodopa.
[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of levodopa.
Use in combination may result in additive central nervous system depression and
MONITOR: Limited clinical data suggest that high protein content in the diet may reduce or cause fluctuations in the clinical response to levodopa in patients with Parkinson's disease.
Proposed mechanisms include delayed gastric emptying, decreased levodopa absorption when taken with a protein rich diet, and competition with certain amino acids for transport across the gut wall and Data have been conflicting. Clinical studies have variously reported no effect, reduced levodopa absorption with low-protein meals, reduced effects of levodopa with high daily protein intake, and no differences compared to fasting with high-protein meals. Neuroleptic malignant-like symptoms were reported in a patient with Parkinson's disease who was receiving pramipexole, entacapone, and immediate-release levodopa Another patient receiving immediate-release carbidopa Until more data are available, it is advisable to avoid large fluctuations in daily protein intake and to monitor patients for altered effects of levodopa if the protein content of the diet is increased.
MANAGEMENT: In general, alcohol consumption should be avoided or limited during treatment with CNS-depressant agents.
L-DOPA Drug Interaction
Moderate: rasagiline, rasagiline, quetiapine, quetiapine, valproic acid, valproic acid, pyridoxine, pyridoxineUnknown: 5-hydroxytryptophan, 5-hydroxytryptophan, ginkgo, ginkgo, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol
L-DOPA Disease Interaction
Major: cardiac disease, hypotension, neuroleptic malignant syndrome, psychoses/depression, psychosis, glaucoma, liver/renal, melanoma, reactive airway diseaseModerate: GI bleeding
Volume of Distribution
168L for orally inhaled levodopa.
Elimination Route
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.
Half Life
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.
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. When given carbidopa, the clearance of levodopa was 5.8mL/min/kg in elderyly patients and 9.3mL/min/kg in younger patients.
Elimination Route
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
Innovators Monograph
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