Levodopa distribution

FIGURE 29-2. Levodopa absorption and metabolism. Levodopa is absorbed in the small intestine and is distributed into the plasma and brain compartments by an active transport mechanism. Levodopa is metabolized by dopa decarboxylase, monoamine oxidase, and catechol-O-methyltransferase. Carbidopa does not cross the blood-brain barrier. Large, neutral amino acids in food compete with levodopa for intestinal absorption (transport across gut endothelium to plasma). They also compete for transport across the brain (plasma compartment to brain compartment). Food and anticholinergics delay gastric emptying resulting in levodopa degradation in the stomach and a decreased amount of levodopa absorbed. If the interaction becomes a problem, administer levodopa 30 minutes before or 60 minutes after meals. 

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). 

Following absorption from the gastrointestinal tract, levodopa is rapidly converted to dopamine by the enzyme dopa decarboxylase. This enzyme is distributed extensively throughout the body and can be found in locations such as the liver, intestinal mucosa, kidneys, and skeletal muscle. Conversion of 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... 

Fig. 25.7. Diagrammatic representation of the peripheral decarboxylation of levodopa to form dopamine (DA) and the mode of action of extracerebral decarboxylase on levodopa metabolism and distribution in vivo. The concurrent administration of levodopa and a decarboxylase inhibitor decreases the amount of levodopa required to elicit a therapeutic response in parkinsonism. HVA, homovanillic acid.

Carter JH, Nutt JG, Woodward WR Hatcher LF, Trotman TL. Amount and distribution of dietary protein affects clinical response to levodopa in Parkinson s disease. Neurology (1989)... 

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