Carbidopa

226.23

226.23

249-271-9

KR87B45RGH

751137

DTXSID4022735

C61803

N04BA03|N04BA02

2932999099

116

-2.2

Solid

1.4±0.1 g/cm3

208 °C

528.7±50.0°C at 760 mmHg

273.5±30.1 °C

1.641

3.8 mg/L

-20ºC

5.27E-12mmHg at 25°C

2.3None

2.3

142.4 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

NONH for all modes of transport

3

MW5298000

P261, P264, P270, P271, P273, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501

H302

|Danger|H315 (86.11%): Causes skin irritation [Warning Skin corrosion/irritation]|P201, P202, P261, P264, P271, P280, P281, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 74 companies from 9 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Warning|H302 (52.22%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P273, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 90 companies from 9 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H341 (100%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]|P201, P202, P281, P308+P313, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

The LD50 of carbidopa is reported to be in the rat of 4810 mg/kg.[MSDS] In animal studies, carbidopa showed no incidences on neoplasia and showed no effect on the fertility status and development. No reports of overdosage have been registered with the carbidopa-only product. In the event of overdosage, immediate gastric lavage is recommended as well as intravenous fluid administration. Continuous electrocardiographic monitoring is required.

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.

It is widely accepted that the protein binding of carbidopa is 76%. However, more studies are required or the presentation of the source of this information.

Carbidopa is indicated with [levodopa] for the treatment of symptoms of idiopathic Parkinson disease, postencephalitic parkinsonism and symptomatic parkinsonism followed by carbon monoxide or manganese intoxication. The combination therapy is administered for the reduction of [levodopa]-driven nausea and vomiting. The product of carbidopa should be used in patients where the combination therapy of carbidopa/[levodopa] provide less than the adequate daily dosage. As well carbidopa can be used in patients where the dosages of carbidopa and [levodopa] require individual titration.|FDA Label|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

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.

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.)|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.)|Compounds and drugs that block or inhibit the enzymatic action of AROMATIC AMINO ACID DECARBOXYLASES. Pharmaceutical agents in this category are used in conjunction with LEVODOPA in order to slow its metabolism. (See all compounds classified as Aromatic Amino Acid Decarboxylase Inhibitors.)

When [levodopa]/carbidopa is administered orally, 40-70% of the administered dose is absorbed. Once absorbed, carbidopa shows bioavailability of 58%. A maximum concentration of 0.085 mcg/ml was achieved after 143 min with an AUC of 19.28 mcg.min/ml.|In animal studies, 66% of the administered dose of carbidopa was eliminated via the urine while 11% was found in feces. These studies were performed in humans and it was observed a urine excretion covering 50% of the administered dose.|The volume of distribution reported for the combination therapy of carbidopa/[levodopa] is of 3.6 L/kg. However, carbidopa is widely distributed in the tissues, except in the brain. After one hour, carbidopa is found mainly in the kidney, lungs, small intestine and liver.|The reported clearance rate for the combination therapy of [levodopa]/carbidopa is 51.7 L/h.

The loss of the hydrazine functional group (probably as molecular nitrogen) represents the major metabolic pathway for carbidopa. There are several metabolites of carbidopa metabolism including 3-(3,4-dihydroxyphenyl)-2-methylpropionic acid, 3-(4-hydroxy-3-methoxyphenyl)-2-methylpropionic acid, 3-(3-hydroxyphenyl)-2-methylpropionic acid, 3-(4-hydroxy-3-methoxyphenyl)-2-methyllactic acid, 3-(3-hydroxyphenyl)-2-methyllactic acid, and 3,4-dihydroxyphenylacetone (1,2).

The reported half-life of carbidopa is of approximately 107 minutes.

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.

Carbidopa

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