Carbidopa inhibits levodopa decarboxylation process of peripheral tissues, without penetrating the blood-brain barrier and does not affect the conversion of levodopa to dopamine in the central nervous system. Thus, the combination of carbidopa and levodopa allows to increase the amount of levodopa, coming into the brain. When combined ingestion of carbidopa levodopa bioavailability doubles. Introduction carbidopa never results in complete inhibition of dopa decarboxylase. Levodopa halotestin side effects absorbed by active transport from the gastrointestinal tract, its passage through the blood-brain barrier is also carried out by active mechanisms. Barriers to absorption of levodopa is the presence of dopa decarboxylase in the intestinal wall. Levodopa is absorbed from the stomach in a limited amount. The rate of gastric emptying plays a key role in the absorption of the drug. Factors that slow gastric emptying delaying the passage of the drug into the duodenum, and slow its absorption. The maximum concentration of the drug in the blood observed after 1-2 hours after administration. Levodopa penetrates through the blood-brain barrier by facilitated diffusion. The endothelium of the brain capillaries also contains a dopa decarboxylase as a second potential barrier to receipt of levodopa to the brain, however, in these capillaries is decarboxylated small part. With increasing doses of levodopa, the amount of drug in the intestine undergoes decarboxylation decreases.Levodopa is not bound to plasma proteins. The decarboxylation of levodopa dopa decarboxylase is the main way of the formation of dopamine levodopa. A large number of this enzyme in the intestine, liver and kidneys. Methoxylation levodopa influenced by catechol-O-methyltransferase to form a 3-O-is the second metildofy by metabolism of levodopa. With long-term treatment of this metabolite may accumulate. Transamination is an additional route of metabolism of levodopa. The end product of this pathway is vinilpiruvat, vinyl acetate, and 2,4,5-trigidroksifeniluksusnaya acid. All pathways except transamination are irreversible. Isolation: In combination with carbidopa, levodopa half-life is increased to 3 hours. Up to 69% of levodopa can be detected in the urine of a human dopamine and its metabolites -. Vanilinmindalnoy acid, norepinephrine, homovanillic acid digidrofeniluksusnoy acid .
- Hypersensitivity to the drug
- closure glaucoma form
- severe psychosis or neurosis
- Pregnancy and lactation
- melanoma or suspected it
- skin disease of unknown etiology
- Huntington’s disease
- essential tremor
- concomitant use of non-selective MAO inhibitors, an interval of less than 2 weeks after discontinuation of MAO inhibitors
should not be used for the treatment of secondary parkinsonism caused by the use of antipsychotic drugs (neuroleptics).Do not assign patients up to 18 years.
The drug is taken with caution in patients with erosive and ulcerative lesions of gastric and / or duodenal ulcer, a history of epileptic seizures, severe diseases of the cardiovascular system (including myocardial infarction with cardiac arrhythmias in the history of, heart failure), endocrine disorders system (including diabetes), severe lung disease (including asthma), mental disorders, as well as severe liver and kidney function.Dosing and Administration
Inside, a small amount of food or after a meal, with water and without chewing. Since there is competition between the aromatic amino acids and levodopa by sucking, while use of the drug should avoid consuming large amounts of protein. The average daily dose of carbidopa required to inhibit peripheral conversion of levodopa, is 70-100 mg. Exceeding 200 mg carbidopa does not entail further enhance the therapeutic effect. The daily dose of levodopa should not exceed 2000 mg. Initial dose – 2 1/2 tablet twice a day, it is possible to increase the half pill daily as needed. Typically, at the beginning of substitution therapy, the daily dose should not exceed 3 tablets per day (1st tablet 3 times a day). The use of this dosage is recommended in the early treatment of severe cases of Parkinson’s disease. The daily dose of the drug as an exception may be raised during monotherapy, but should not exceed 8 tablets (1 tablet minutes 8 times a day). The use in an amount more than 6 tablets per day should be carried out with great care.
Side effects: Nervous system: Dyskinesia, including choreoathetosis, dystonia, prolonged use syndrome “on-off”, neuroleptic malignant syndrome, dizziness, ataxia, nausea, dystonic involuntary movements, seizures, anorexia, sedation, drowsiness, confusion, nightmares dreams, nervousness, irritability, anxiety, insomnia; altered mental status, including paranoid effects and halotestin side effects transient psychoses;hallucinations, depression with the development of suicidal ideation or without, hypomania, increased libido, euphoria, dementia. The basis for the decision to reduce the dose of the drug may be early symptoms such as muscle twitching and blepharospasm. It reported on the development of seizures, but a direct connection with the reception of the drug carbidopa / levodopa have not been established.Gastrointestinal tract: anorexia, nausea, vomiting, constipation, epigastric pain, dysphagia, dark saliva, ulcerogenic effect in susceptible patients; . rare – gastrointestinal bleeding Cardiovascular system:orthostatic hypotension, collapse, arrhythmias, tachycardia, hypertension, phlebitis. hemopoietic system: rarely – leukopenia, anemia (including haemolytic), thrombocytopenia, agranulocytosis. Allergic reactions: angioneurotic edema, urticaria, skin rashes, itching of the skin, the disease Henoch-Schönlein. Changes in laboratory parameters: changes in the level of alanine transferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, urea nitrogen, bilirubin, iodine-related protein, hyperuricemia, giperkreatinemiya, positive direct Coombs sample. Others: syncope, chest pain, mydriasis, diplopia, dyspnea, darkening secretions of sweat glands, dark urine, increase or reduction of body weight. Side effects are usually dependent on the received dosage, as well as on the individual sensitivity of the patient. Side effects can be eliminated temporary dose reduction without interruption in treatment. If side effects do not regress, the treatment should be stopped gradually.
Other side effects that occurred in patients receiving levodopa, which should be considered in the case of the drug carbidopa / levodopa: Gastrointestinal tract: dyspepsia, dry mouth, feeling of bitterness in the mouth, sialoreya, dysphagia, bruxism, hiccups, pain and discomfort abdominal pain, constipation, flatulence, burning sensation of language. Metabolism: decrease or increase in body weight, edema. Central nervous system: weakness, fainting, fatigue, headache, asthenia, decreased mental activity, disorientation, ataxia, numbness, increased hand tremor, muscle convulsions, trismus, activation of latent syndrome Bernard-Horner, insomnia, anxiety, euphoria, agitation, unsteadiness of gait. Special senses: diplopia, blurred vision, dilated pupils, oculogyric crises. Urogenital: urinary retention, urinary incontinence, priapism. Other side effects: hoarseness, malaise, “tides” of blood to the face skin, neck and chest, dyspnea, malignant melanoma. Reported decrease in hemoglobin and hematocrit, hyperglycemia, leukocytosis, bacteriuria eritrotsiturii. Changes in laboratory parameters: preparations containing carbidopa-levodopa, can cause false positive reactions to ketone bodies in urine, for the determination of ketonuria if used test strips. This reaction is not changed by boiling the urine sample. False halotestin side effects negative results can be obtained using the glucose oxidase method for determining glycosuria.