CARBIDOPA/ LEVODOPA

Indications

• Parkinson's disease
• Parkinsonian syndromes

Dosage

Children: The use of carbidopa in children is not well established; therefore, paediatric dosing should be determined by a specialist and tailored to the individual child's needs, closely

Adults: The recommended dosage of carbidopa is typically 75 mg to 200 mg per day, administered in divided doses based on the combination with levodopa. The specific dosage should be guided by individual patient response and tolerability.

Mechanism of action

Carbidopa inhibits the enzyme aromatic L-amino acid decarboxylase (DDC), which is essential for the metabolism of levodopa in the periphery. By inhibiting DDC, carbidopa prevents the conversion of levodopa to dopamine outside the brain, allowing more levodopa to cross the blood-brain barrier where it can be converted to dopamine. This mechanism enhances the effectiveness of levodopa therapy in treating Parkinson's disease.

Pharmacodynamics

Carbidopa increases the bioavailability of levodopa by inhibiting its metabolism in the gastrointestinal tract and the periphery. This results in higher plasma levels of levodopa, which can enhance dopaminergic activity in the brain. The combination of carbidopa and levodopa has shown to increase the half-life of levodopa significantly, leading to improved clinical outcomes in patients with Parkinson's disease.

Pharmacokinetics

Carbidopa is not significantly absorbed from the gastrointestinal tract when taken alone and does not cross the blood-brain barrier. When administered with levodopa, it enhances levodopa's absorption and bioavailability, allowing more levodopa to enter the central nervous system. The half-life of carbidopa is approximately 1.5 hours, and it is primarily excreted unchanged in the urine.

Adverse effects

• Nausea
• Vomiting
• Dizziness
• Headache
• Dry mouth
• Constipation
• Orthostatic hypotension
• Dyskinesia
• Confusion
• Hallucinations

Interactions

• Iron salts may reduce the absorption of carbidopa/levodopa
• Antipsychotics may counteract the effects of levodopa
• MAO inhibitors can increase the risk of hypertensive crisis when combined with levodopa

Precautions

• Use with caution in patients with a history of psychotic disorders
• Monitor for the development of dyskinesias
• Caution in patients with severe cardiovascular disease
• Risk of melanoma has been reported; monitor skin changes

Pregnancy

Carbidopa is classified as category C, meaning risk cannot be ruled out. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether carbidopa is excreted in human milk. Caution should be exercised when administered to a nursing woman.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets
• Extended-release tablets

Mechanism of action

Carbidopa is an inhibitor of the DDC which in order, inhibits the peripheral metabolism of levodopa. DDC is very important in the biosynthesis of L-tryptophan to serotonin and the modification of L-DOPA to dopamine. DDC can be found in the body periphery and in the blood-brain barrier. The action of carbidopa is focused on peripheral DDC as this drug cannot cross the blood-brain barrier. Hence, it will prevent the metabolism of [levodopa] in the periphery but it will not have any activity on the generation of dopamine in the brain.

Pharmacodynamics

When mixed with [levodopa], carbidopa inhibits the peripheral conversion of [levodopa] to dopamine and the decarboxylation of [oxitriptan] to serotonin by aromatic L-amino acid decarboxylase. This results in an increased amount of [levodopa] and [oxitriptan] available for transport to the central nervous system. Carbidopa also inhibits the metabolism of [levodopa] in the GI tract, thus, increasing the bioavailability of [levodopa]. The presence of additional units of circulating [levodopa] can increase the effectiveness of the still functional dopaminergic neurons and it has been shown to alleviate symptoms for a time. The action of carbidopa is very important as [levodopa] is able to cross the blood-brain barrier while dopamine cannot. Hence the administration of carbidopa is essential to prevent the transformation of external [levodopa] to dopamine before reaching the main action site in the brain. The coadministration of carbidopa with [levodopa] has been shown to increase the half-life of [levodopa] more than 1.5 times while increasing the plasma level and decreasing clearance. The combination therapy has also shown an increase of the recovery of [levodopa] in urine instead of dopamine which proves a reduced metabolism. This effect has been highly observed by a significant reduction in [levodopa] requirements and a significant reduction in the presence of side effects such as nausea. It has been observed that the effect of carbidopa is not dose-dependent.