ADMET-Absorption, Distribution, Metabolism, Excretion, and Toxicity

StatusFDA approved
AdministrationN/A
PharmacologyA naturally-occurring dietary supplement and psychoactive drug found in certain kinds of food and herbs (e.g. Mucuna pruriens, or velvet bean), and is synthesized from the essential amino acids L-phenylalanine (PHE) and L-tyrosine (TYR) in the mammalian body and brain.

Absorption_value86.0
Absorption (description)Levodopa is rapidly absorbed from the small bowel after oral administration and widely distributed in the tissues; less than 1% of a dose reaches the brain.
Caco_2N/A
Bioavailability41.0

MetabollsmIt is extensively metabolised, mainly by decarboxylation to dopamine which is further metabolised, and also by methylation to 3-O-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 [norepinephrine], 3-methoxytyramine, and to the two major excretory metabolites, 3,4-dihydroxyphenylacetic 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.
Half life1.4 h which may be increased by concomitant administration of peripheral decarboxylase inhibitors; 3-O-methyldopa about 13 h.

ExcretionAbout 70 to 80% of a dose is excreted in the urine in 24 h. Of the material excreted in the urine, about 50% is DOPAC and HVA, 10% is dopamine, up to 30% is 3-O-methyldopa, and less than 1% is unchanged drug. Less than 1% of a dose is eliminated in the faeces. During prolonged therapy the ratio of the amount of DOPAC produced to that of HVA may be increased.
Urinary Excretion<1
Clerance23 ml/min/kg