Madopar

Absorption

Low levels of endogenous levodopa are detectable in pre-dose blood samples. After oral administration of Madopar, levodopa and benserazide are rapidly absorbed, mainly in the upper regions of the small intestine and absorption there is independent of the site. Interaction studies indicate that a higher proportion of levodopa is absorbed when administered in combination with benserazide, compared with levodopa administered alone. 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 absorption (AUC) increase proportionally with dose (50 - 200 mg levodopa). The peak levodopa plasma concentration is 30% lower and occurs later when Madopar is administered after a standard meal. Food intake generally reduces the extent of levodopa absorption by 15% but this can be variable.

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 approximately 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 the 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 (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 small extent in faeces (24%).

• R52.1 – Chronic intractable pain
• R52.2 – Other chronic pain
• R52.9 – Unspecified pain

Capsule contents:

Microcrystalline cellulose (E460)

Povidone K90 (E1201)

Talc (E553b)

Magnesium stearate (E572)

Mannitol (E421)

Capsule shell:

Gelatin

Indigo carmine (E132)

Titanium dioxide (E171)

Iron oxide (E172)

Printing Ink:

Black iron oxide (E172)

None known

3 years.

Do not store above 25°C. Store in the original package. Keep bottle tightly closed.

Amber glass bottles with polyethylene closure with integrated desiccant containing 100 capsules.

Dispose of the medication in accordance with local regulations for medical waste.

Roche Products Limited, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, United Kingdom.

PL 00031/0074

Date of last renewal: 6 July 2003

10 March 2016

• R52.1 – Chronic intractable pain
• R52.2 – Other chronic pain
• R52.9 – Unspecified pain

• R52.1 – Chronic intractable pain
• R52.2 – Other chronic pain
• R52.9 – Unspecified pain