Doparl

Uses

Doparl 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.

Doparl 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. Doparl 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.

Doparl 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 Doparl works

Doparl 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. Doparl may lower prolactin and interfere with lactation but there is limited human data to demonstrate this effect. Doparl 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
MANAGEMENT: In general, alcohol consumption should be avoided or limited during treatment with CNS-depressant agents.

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.

Doparl 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

Doparl 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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