Tidomet/Tidomet CR Mechanism of Action

Pharmacology: Pharmacodynamics: The symptoms of Parkinson's disease are related to depletion of dopamine in the corpus striatum. Administration of dopamine is ineffective in such patients because dopamine does not cross the blood brain barrier. However, levodopa, the precursor, of dopamine, does not cross the blood brain barrier and is converted to dopamine in the basal ganglia/brain. When levodopa is administered orally, it is rapidly converted to dopamine in non-neuronal tissues especially intestinal mucosa so that only a small portion of the given dose is transported unchanged to the neuronal tissue. As a consequence large doses of levodopa are required to be administered to produce adequate therapeutic effect which may often be associated with side effects. Combination of levodopa with a selective peripheral decarboxylase inhibitor, carbidopa can almost completely abolish extra cerebral metabolism of levodopa and in oral doses of 10-25 mg may reverse the effects of levodopa by increasing the rate of decarboxylation. Carbidopa inhibits the action of pyridoxine.
Tidomet CR: When levodopa is administered orally, it is rapidly decarboxylated to dopamine in extracerebral tissues so that only small portion of a given dose is transported unchanged in the central nervous system. Since levodopa competes with certain amino acids for transport across the gut wall, the absorption of levodopa may be impaired in some patients on a high protein diet.
Carbidopa inhibits decarboxylation of peripheral levodopa. It does not cross the blood brain barrier and does not affect the metabolism of levodopa within the central nervous system. Decarboxylase inhibiting activity of Carbidopa is limited to extracerebral tissues; hence the administration of carbidopa with levodopa makes more levodopa available to transport to the brain.
Controlled release preparation is designed to release Carbidopa 50 mg and Levodopa 200 mg over 4 to 6 hours period, there is a less variation in plasma levodopa levels than with the conventional formulation.
Pharmacokinetics: Carbidopa reduces the amount of levodopa required to produce a given response by about 75% and, when administered with levodopa, increases both plasma levels and the plasma half life of levodopa, and decreases plasma and urinary dopamine and homovanillic acid.
Elimination half life of levodopa in the presence of carbidopa is about 1.5 hours. Tidomet in controlled release preparation have an apparent half life of levodopa may be prolonged because of continuous absorption. The mean time to peak concentration of levodopa after a single dose of co-careldopa controlled release preparation is about 2 hours as compared to 0.5 hours after conventional administration. The maximum concentration and extent availability of levodopa after a single dose of co-careldopa controlled release is about 35% and 70-75% respectively compared to conventional formulation. At steady state, carbidopa bioavailability from co-careldopa controlled release is approximately 58% relative to that from conventional formulation.