Absorption
After oral administration of Madopar, levodopa and benserazide are mainly absorbed from the upper regions of the small intestine and absorption there is independent of the site. Maximum plasma concentrations of levodopa are reached approximately one hour after ingestion of Madopar. The absolute bioavailability of levodopa from standard Madopar is approximately 98%.
The maximum plasma concentration of levodopa and the extent of levodopa absorption (AUC) increase proportionally with dose (50 – 200mg levodopa).
Food intake reduces the rate of levodopa absorption. The peak levodopa plasma concentration is 30% lower and occurs later when Madopar is administered after a standard meal. The extent of levodopa absorption is reduced by 15%.
Distribution
Levodopa crosses the blood-brain barrier by a saturable transport system. It is not bound to plasma proteins. Benserazide does not cross the blood-brain barrier at therapeutic doses. Benserazide is concentrated mainly in the kidneys, lungs, small intestine and liver.
Metabolism
The 2 major routes of metabolism of levodopa are decarboxylation to form dopamine, which in turn is converted to a minor degree to norepinephrine, and to a greater extent, to inactive metabolites, and O-methylation, forming 3-O-methyldopa, which has an elimination half-life of approx. 15 hours and accumulates in patients receiving therapeutic doses of Madopar.
Decreased peripheral decarboxylation of levodopa when it is administered with benserazide is reflected in higher plasma levels of levodopa and 3-O-methyldopa.
Benserazide is hydroxylated to trihydroxybenzylhydrazine in the intestinal mucosa and liver. This metabolite is a potent inhibitor of the aromatic amino acid decarboxylase.
Elimination
In the presence of the peripheral decarboxylase inhibitor, benserazide, the elimination half-life of levodopa is approximately 1.5 hours. In elderly patients the elimination half-life is slightly (approx. 25%) longer. Clearance of levodopa is 430ml/min. Benserazide is almost entirely eliminated by metabolism. The metabolites are mainly excreted in the urine (64%) and to a smaller extent in the faeces (24%).
Absorption
After oral administration of Madopar, levodopa and benserazide are mainly absorbed from the upper regions of the small intestine and absorption there is independent of the site. Maximum plasma concentrations of levodopa are reached approximately one hour after ingestion of Madopar. The absolute bioavailability of levodopa from standard Madopar is approximately 98%.
The maximum plasma concentration of levodopa and the extent of levodopa absorption (AUC) increase proportionally with dose (50 – 200mg levodopa).
Food intake reduces the rate of levodopa absorption. The peak levodopa plasma concentration is 30% lower and occurs later when Madopar is administered after a standard meal. The extent of levodopa absorption is reduced by 15%.
Distribution
Levodopa crosses the blood-brain barrier by a saturable transport system. It is not bound to plasma proteins. Benserazide does not cross the blood-brain barrier at therapeutic doses. Benserazide is concentrated mainly in the kidneys, lungs, small intestine and liver.
Metabolism
The 2 major routes of metabolism of levodopa are decarboxylation to form dopamine, which in turn is converted to a minor degree to norepinephrine, and to a greater extent, to inactive metabolites, and O-methylation, forming 3-O-methyldopa, which has an elimination half-life of approx. 15 hours and accumulates in patients receiving therapeutic doses of Madopar.
Decreased peripheral decarboxylation of levodopa when it is administered with benserazide is reflected in higher plasma levels of levodopa and 3-O-methyldopa.
Benserazide is hydroxylated to trihydroxybenzylhydrazine in the intestinal mucosa and liver. This metabolite is a potent inhibitor of the aromatic amino acid decarboxylase.
Elimination
In the presence of the peripheral decarboxylase inhibitor, benserazide, the elimination half-life of levodopa is approximately 1.5 hours. In elderly patients the elimination half-life is slightly (approx. 25%) longer. Clearance of levodopa is 430ml/min. Benserazide is almost entirely eliminated by metabolism. The metabolites are mainly excreted in the urine (64%) and to a smaller extent in the faeces (24%).