TIDOMET FORTE TABLET

Indication

For treatment of the symptoms of idiopathic Parkinson's disease (paralysis agitans), post-encephalitic parkinsonism

Mechanism of Action

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 increased amount of levodopa and oxitriptan available for transport to the CNS. Carbidopa also inhibits the metabolism of levodopa in the GI tract, thus, increasing the bioavailability of levodopa.

Pharmacokinetics

Absorption

Rapidly decarboxylated to dopamine in extracerebral tissues so that only a small portion of a given dose is transported unchanged to the central nervous system.

Distribution

Metabolism

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). [PMID: 4150141]

Elimination

Toxicity

Symptoms of a carbidopa toxicity include muscle spasms or weakness, spasms of the eyelid, nausea, vomiting, diarrhea, an irregular heartbeat, confusion, agitation, hallucinations, and unconsciousness.

Active Ingredient/Synonyms

(-)-L-alpha-Hydrazino-3,4-dihydroxy-alpha-methylhydrocinnamic acid monohydrate | (S)-(−)-carbidopa | (S)-carbidopa | (αS)-α-hydrazino-3,4-dihydroxy-α-methylbenzenepropanoic acid | Carbidopa (anhydrous) | Carbidopa anhydrous | Carbidopum | L-3-(3,4-dihydroxyphenyl)-2-methyl-2-hydrazinopropionic acid | L-α-methyldopahydrazine | Carbidopa |

Indication

For the treatment of idiopathic Parkinson's disease (Paralysis Agitans), postencephalitic parkinsonism, symptomatic parkinsonism which may follow injury to the nervous system by carbon monoxide intoxication, and manganese intoxication.

Mechanism of Action

Striatal dopamine levels in symptomatic Parkinson's disease are decreased by 60 to 80%, striatal dopaminergic neurotransmission may be enhanced by exogenous supplementation of dopamine through administration of dopamine's precursor, levodopa. A small percentage of each levodopa dose crosses the blood-brain barrier and is decarboxylated to dopamine. This newly formed dopamine then is available to stimulate dopaminergic receptors, thus compensating for the depleted supply of endogenous dopamine.

Pharmacokinetics

Absorption

Levodopa is rapidly absorbed from the proximal small intestine by the large neutral amino acid (LNAA) transport carrier system.

Distribution

Metabolism

95% of an administered oral dose of levodopa is pre-systemically decarboxylated to dopamine by the L-aromatic amino acid decarboxylase (AAAD) enzyme in the stomach, lumen of the intestine, kidney, and liver. Levodopa also may be methoxylated by the hepatic catechol-O-methyltransferase (COMT) enzyme system to 3-O-methyldopa (3-OMD), which cannot be converted to central dopamine.

Elimination

Toxicity

Oral, mouse: LD₅₀ = 2363 mg/kg; Oral, rabbit: LD₅₀ = 609 mg/kg; Oral, rat: LD₅₀ = 1780 mg/kg.

Active Ingredient/Synonyms

(−)-3-(3,4-dihydroxyphenyl)-L-alanine | (−)-dopa | 3-Hydroxy-L-tyrosine | 3,4-Dihydroxy-L-phenylalanine | Dihydroxy-L-phenylalanine | L-3,4-dihydroxyphenylalanine | L-beta-(3,4-Dihydroxyphenyl)alanine | L-DOPA | Levodopum | β-(3,4-dihydroxyphenyl)-L-alanine | β-(3,4-dihydroxyphenyl)alanine | Levodopa |