Levodopa

Carbidopa
Justin Favero
Psych 3740
Parcopa
Carbidopa / Levodopa
! Parcopa is a combination of two drugs, carbidopa/levolevodopadopa, used to
treat Parkinsonʼs disease. Parkinsonʼs is a progressive disease that affects mainly
extrapyramidal movement. Symptoms of this disease are secondary to a decreased
level of dopamine in the central nervous system. Some common signs of this disease
include rigidity, shaking when at rest, and difficulty to start and follow through with a
movement. When administered, carbidopa/levodopa are either given in a 50mg of
Carbidopa to 200mg of Levodopa combination or with a combination of either 25/100,
10/100, or 25/250 depending on individual patient needs and established effective
dosage (“Parcopa”, 2007). Levodopa is commonly given as a stand alone drug in
Parkinsonʼs patients but is more effective when administered with carbidopa because of
decarboxylation peripherally (“Parcopa”, 2002).
Pharmacodynamics 
# The mechanism of action by which levodopa is able to alleviate Parkinsonʼs
disease symptoms is two fold. Dopamine in the blood is unable to cross the blood brain
barrier into the brain and so dopamine can not simply be taken in its end stage form.
Levodopa is the main metabolic precursor of dopamine and is able to pass the blood
brain barrier. Once it is in the brain, levodopa is converted to dopamine in the basal
ganglia by DOPA decarboxylase (Dorfman, 1992). Dopamine acts on dopaminergic
neurons in the substantia nigra. Via the nigrostriatatial pathway, these dopaminergic
neurons synapse in the striatum of the basal ganglia. More specifically these neurons
synapse in the putamen and caudate nucleus (Dauer, pg 819). The other main factor in
keeping levodopa from reaching the central nervous system is decarboxylase.
Decarboxylase deactivates levodopa by removing a carboxyl group in extracerebral
tissues. This means that much larger therapeutic doses are needed when levodopa is
used alone in order for it to reach the brain. Carbidopa limits decarboxylase from
removing carboxyl groups from levodopa. Carbidopa doesnʼt cross the blood brain
barrier however so its action is only in the extracerebral tissues. Thus when taken
together, carbidoba allows more levodopa to cross the blood brain barrier and into the
CNS (“Carbidopa and Levodopa”, 2009).
Pharmacokinetics
# Oral administration is the only route of administration utilized with Parcopa and
with all carbidopa/levodopa drugs. Most commonly the tablet is fast dissolving and can
be placed on the tongue without any extra liquid. Therapeutic dosage should be
established over a number of weeks by evaluating effectiveness in symptom alleviation
(“Parcopa”, 2007). Levodopa is one of many amino acids trying to cross the gut into the
circulatory system in the intestines. For this reason, high protein diets can cause
decreased levodopa adsorption (Threlkeld, 1998). Other than protein, iron has been
shown to also decrease the bioavailability of levodopa. Iron forms many complexes with
many drugs although the exact interaction is not fully understood (Campbell, 1991).
Vitamin B6 also causes increased decarboxylation rates especially of amino acids such
as levodopa. Carbidoba largely neutralizes this effect however and accordingly the
vitamin can continue to be supplemented when necessary. The stand alone half-life of
levodopa is approximately 50 minutes but when taken with carbidopa this half-life jumps
up to an hour and a half. Besides increasing the half-life, carbidopa decreases the
amount of levodopa needed to reach an effective dose by over 75 percent (“Parcopa”,
2007). Liver functioning is not frequently effected and increases in bilirubin and alkaline
phosphate levels in the blood are rare. Excretion of levodopa is mainly through the urine
and 80% of the prescribed dose is excreted within 24 hours. Little to none is found
remaining in the feces (Dorfman, 1992). and Routes of administration, absorption,
distribution, solubility, half-life, hepatic effects, and excretion.

# Side effects: Dyskinesia, or involuntary and repetitive motions, is one of the

most commonly occurring side effects from carbidopa/levodopa based drugs.
Decreasing the dose will usually help keep these movements in control. Less frequently
occurring side effects in order of appearance include nausea, hallucinations, confusion,
dizziness, and depression (“Carbidopa and Levodopa”, 2009).
# Cost: Depending on the strength of the drug, prices can range from 100 dollars
per hundred pills to over 200 dollars for every hundred pills (Pharmacychecker.com).
# Alternative treatments: Acupuncture, biofeedback, aromatherapy, exercise,
vitamin supplementation, hypnosis, massage, and herbal concoctions are all considered
alternative treatments. When considering alternative treatments one must remember
that these are procedures and or claims that have not been proven empirically. Out of
these alternatives, vitamin E supplementation has received the most publicity. Vitamin E
has been suggested mainly because of its large sphere of benefits. Vitamin E acts as
an antioxidant, increases production of red blood cells, and promotes general health,
growth, and proper functioning (Haines, 2005).

References
Campbell NR, Hasinoff BB (1991). Iron supplements: a common cause of drug
# # interactions. Brit J Clin Pharmacol 1991;31:251-5.
Carbidoba and Levodopa (2009). Retrieved February 28, 2010, from http://
www.drugs.com/pro/carbidopa-and-levodopa.html
Dauer, W., Przedborski, S. (2003). Parkinson's Disease Mechanisms and Models.
# Neuron, Volume 39, Issue 6, Pages 889-909.
Dorfman, Patricia; Landoni, Julia Higa de (1992). Levodopa. Retrieved February 28,
# 2010, from http://www.inchem.org/documents/pims/pharm/levedopa.htm
Haines, Cynthia Dennison (2009, June). Parkinsonʼs Disease: Alternative Treatments.
# Retrieved February 28, 2010 from http://www.webmd.com/parkinsons-disease/
# alternative-treatments-parkinsons.
Parcopa. (2007). Retrieved February 28, 2010, from http://www.drugs.com/pro/
parcopa.html
PARCOPA™(carbidopa-levodopa orally disintegrating tablets) RX ONLY (2002).
# Retrieved February 28, 2010, from http://www.medicineonline.com/drugs/p/2984/
# PARCOPA-carbidopa-levodopa-orally-disintegrating-tablets-RX-ONLY.html.
Threlkeld DS, ed. Central Nervous System Drugs, Antiparkinson Agents, Levodopa
# (1998, April). In Facts and Comparison Drug Information. St. Louis, MO: Facts
# and Comparisons Drug Information, Apr 1998, 289p-90a.levodopa