Sinemet

Drug interactions

Potentially hazardous interactions with other drugs
Anaesthetics: risk of arrhythmias with volatile liquid anaesthetics such as halothane.
Antidepressants: hypertensive crisis with MAOIs and linezolid (including moclobemide) - avoid for at least 2 weeks after stopping MAOI.
Bupropion: increased risk of side effects of levodopa
Ferrous sulphate: reduces AUC of levodopa by 30-50%, clinically significant in some but not all patients.

Metabolism

Levodopa is rapidly decarboxylated by the enzyme aromatic l-amino acid decarboxylase, mostly in the gut, liver, and kidney, to dopamine, which is metabolised in turn, principally to dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Other routes of metabolism include O-methylation, transamination, and oxidation, producing a variety of minor metabolites including noradrenaline and 3-O-methyldopa; the latter may accumulate in the CNS due to its relatively long half-life.
About 80% of an oral dose of levodopa is excreted in the urine within 24 hours, mainly as dihydroxyphenylacetic and homovanillic acids. Only small amounts of levodopa are excreted unchanged in the faeces.
Carbidopa inhibits the peripheral decarboxylation of levodopa to dopamine. It is rapidly excreted in the urine both unchanged and in the form of metabolites.