hi syber-siblings

there have been a few questions about tolcapone/tasmar recently
so i couldn't resist going out hunting

janet

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ABSTRACT - KURTH ET AL - JANUARY 1997
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Tolcapone improves motor function and reduces levodopa requirement in
patients with Parkinson's disease experiencing motor fluctuations: a
multicenter, double-blind, randomized, placebo-controlled trial. Tolcapone
Fluctuator Study Group I.
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Tolcapone is a potent catechol-O-methyltransferase inhibitor that prolongs
the plasma half-life of levodopa. This multicenter, double-blind,
placebo-controlled study used two 10-hour clinical evaluations to compare
the efficacy and safety of three doses of tolcapone (50, 200, and 400 mg
tid) with placebo in patients with Parkinson's disease (PD) experiencing
motor fluctuations from levodopa/carbidopa. One hundred fifty-one patients
completed the study. Clinical evaluations lasting 10 hours were performed
on day -1 and day 42 using United Parkinson's Disease Rating Scale motor
subscale and "on/off" and dyskinesia assessments every 30 minutes.
Tolcapone significantly reduced "off" time an average of 40% and increased
total "on" time by about 25% at all dose levels, as compared to placebo
treatment. Levodopa/carbidopa dosage and frequency were significantly
reduced. Tolcapone was well tolerated, with patients experiencing typical
dopaminergic side effects that could be reduced or eliminated by lowering
levodopa/carbidopa dosages. Tolcapone was effective at prolonging the
clinical benefit of levodopa and reducing total levodopa requirements in PD
patients with motor fluctuations.

Neurology 1997 Jan;48(1):81-87
Kurth MC, Adler CH, Hilaire MS, Singer C,
Waters C, LeWitt P, Chernik DA, Dorflinger EE, Yoo K
Barrow Neurological Institute, Phoenix, AZ 85013, USA.
PMID: 9008498, MUID: 97161241

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NEWS - REUTERS - JANUARY 1997
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New Parkinson's Disease Treatment
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NEW YORK, Jan 21 (Reuters) -- A new drug may allow people with Parkinson's
disease to live each day on a more even keel, with fewer fluctuations in
their symptoms, according to researchers.

Patients with the disorder also need less of the main medication for
Parkinson's -- levodopa -- when the drug tolcapone is added to their
treatment. The new drug works by slowing the metabolism, or break down, of
levodopa, thus prolonging its availability to the body.

"This is an important development in the treatment of Parkinson's disease,"
says Dr. Mathias Kurth, a neurologist with Barrow Neurological Institute in
Phoenix, Arizona.

"This is another step toward making treatment better and smoother and
making life better for patients," he adds.

The Barrow Neurological Institute is one of several medical centers around
the nation involved in the Tolcapone Fluctuation Study Group. Others
include the Mayo Clinic, Scottsdale, Arizona; Boston University, Boston,
Massachusetts; the University of Miami, Florida; the University of Southern
California, Los Angeles; and Sinai Hospital of Detroit, Michigan.

The study included 151 Parkinson's patients who each day experienced "off"
periods of muscle slowness, rigidity, and trembling of the arms and legs,
and "on" periods of relatively normal functioning when their levodopa
dosage was working.

In a report published in January's issue of Neurology, the researchers note
that tolcapone reduced patients' "off" time by an average of 40% and
increased their total "on" time by about 25%. Patients taking tolcapone
also needed fewer doses of levodopa.

Neurologists have known for some time that levodopa works well when it is
first given to Parkinson's patients. The drug is converted by the body into
dopamine, a nerve transmitter substance that reduces muscle tone so that
movement is not jerky.

In Parkinson's patients, dopamine levels are diminished in the parts of the
brain -- collectively known as the basal ganglia -- affected by the disease.

But after a time, the beneficial effects of levodopa often suddenly wear
off, and other drugs must be given as substitutes.

According to the researchers, tolcapone prolongs the effect of levodopa by
blocking an enzyme that breaks down and converts levodopa to an inactive
substance. This allows levodopa to remain in the bloodstream longer.

Side effects of tolcapone observed in the study include nausea and abnormal
muscle movements (uncontrollable twitches and jerks). But the researchers
note these can be lessened or eliminated by adjusting the dose of levodopa.

Tolcapone's maker is Hoffman-La Roche, of Nutley, New Jersey. The drug
company expects to obtain Food and Drug Administration approval for
tolcapone some time this year.

According to the American Academy of Neurology in Minneapolis, Parkinson's
disease affects more than 800,000 people in the U.S., with about 50,000 new
cases diagnosed each year.

SOURCE: Neurology (1997;48:81-87)
Copyright 997 Reuters Limited.
<http://www.reutershealth.com/news/rhdn/199701/1997012104.html>

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AMERICAN ACADEMY OF NEUROLOGY - ADLER ET AL - APRIL 1997
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New Drug Improves On-Off Periods in PD              April 17, 1997
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Clinical results presented at the American Academy of Neurology annual
meeting in Boston indicate that tolcapone (Tasmar, Roche) is effective in
patients with Parkinson's disease suffering from on-off periods. Tolcapone
is the most potent and selective inhibitor of COMT, the enzyme that
metabolizes levodopa peripherally, discovered to date.

In a double-blind, placebo-controlled trial of 215 patients, Adler et al.
found that tolcapone reduced off periods by 30-37%, even as daily levodopa
requirements were reduced by 36-46%. Tolcapone was well tolerated, with
only 3-5% of patients withdrawing from the study because of adverse effects.

Study results are similar to those reported in the Jan. Neurology (1997;
48: 81-7).

<http://pharminfo.com/pubs/pnn/pnn9.html#8>

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ABSTRACT - YAMAMOTO ET AL - 1997
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Effects of tolcapone, a catechol-O-methyltransferase inhibitor, on motor
symptoms and pharmacokinetics of levodopa in patients with Parkinson's
disease.
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The effects of tolcapone, a catechol-O-methyltransferase inhibitor, on the
bioavailability and efficacy of levodopa were evaluated in 12 patients with
Parkinson's disease (PD), 8 of whom showed signs of daily motor
fluctuations (wearing-off phenomenon). Motor disabilities were assessed in
12 patients at 7 time points before and after the chronic administration of
tolcapone using the Unified Parkinson's Disease Rating Scale (UPDRS). The
UPDRS score was improved at all points of determination. Eight patients
with wearing-off phenomenon on levodopa showed symptomatic improvement on
the combination. The area under the curve (AUC) for levodopa increased by
34% (p = 0.0059) after the administration of tolcapone. The elimination
half-life (T1/2) of levodopa was significantly prolonged by 81% (p =
0.0001) after the treatment. The AUC of 3-O-methyldopa, a metabolite of
levodopa, was decreased by 79% (p = 0.0001) and the Cmax (maximum
concentration) was also decreased by 80%d after the administration (p =
0.0001) of tolcapone. The combination of tolcapone and levodopa was well
tolerated. Our findings suggest that tolcapone improves the
pharmacokinetics of levodopa in plasma and motor symptoms of fluctuating PD
patients. It is suggested that tolcapone may be useful drug adjunct to
levodopa in treating patients with PD

J Neural Transm 1997;104(2-3):229-236
Yamamoto M, Yokochi M, Kuno S, Hattori Y, Tsukamoto Y, Narabayashi H, Tohgi
H, Mizuno Y, Kowa H, Yanagisawa N, Kanazawa I
Department of Neurology, Kagawa Prefectural Central Hospital, Japan.
PMID: 9203084, MUID: 97346667

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