Carbidopa excretion

Pharmacokinetics Carbidopa is rapidly and completely absorbed from the GI tract. Widely distributed. Excreted primarily in urine. Levodopa is converted to dopamine. Excreted primarily in urine. Half-life 1-2 hr (carbidopa) 1-3 hr (levodopa). 

Disposition in the Body. Rapidly absorbed from the small bowel after oral administration and widely distributed in the tissues less than 1% of a dose reaches the brain bioavailability about 33%. Extensively metabolised mainly by decarboxylation to dopamine, which is further metabolised, and also by methylation to 3-0-methyldopa which accumulates in the central nervous system most of a dose is decarboxylated by the gastric mucosa before entering the systemic circulation the decarboxylase activity is inhibited by carbidopa and benserazide. Dopamine is further metabolised to noradrenaline, 3-methoxytyramine, and to the two major excretory metabolites, 3,4-dihydroxyphenyl-acetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid, HVA). During prolonged therapy, the rate of levodopa metabolism appears to increase, possibly due to enzyme induction. About 70 to 80% of a dose is excreted in the urine in 24 hours. Of the material excreted in the urine, about 50% is DOPAC and HVA, 10% is dopamine, up to 30% is... 

The greater amount of dopamine that is formed in the brain after orally administered levodopa/carbidopa presumably provides symptomatic relief of parkinsonian symptoms, such as rigidity and bradykinesia. Parkinsonian patients not previously treated with levodopa usually are started on a combination therapy with Sinemet, which is available in a fixed ratio of 1 part carbidopa and 10 parts levodopa. Once formed from levodopa, metabolism of dopamine then proceeds relatively rapidly to the principal excretion products 3,4-dihydroxyphenylacetic acid and 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid) (Fig. 25.2). 

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