Indication |
For the treatment of amyotrophic lateral sclerosis (ALS, Lou Gehrig's Disease) |
Pharmacodynamics |
Riluzole, a member of the benzothiazole class, is indicated for
the treatment of patients with amyotrophic lateral sclerosis (ALS).
Riluzole extends survival and/or time to tracheostomy. It is also
neuroprotective in various in vivo experimental models of
neuronal injury involving excitotoxic mechanisms. The etiology and
pathogenesis of amyotrophic lateral sclerosis (ALS) are not known,
although a number of hypotheses have been advanced. One hypothesis is
that motor neurons, made vulnerable through either genetic
predisposition or environmental factors, are injured by glutamate. In
some cases of familial ALS the enzyme superoxide dismutase has been
found to be defective. |
Mechanism of action |
The mode of action of riluzole is unknown. Its pharmacological
properties include the following, some of which may be related to its
effect: 1) an inhibitory effect on glutamate release (activation of
glutamate reuptake), 2) inactivation of voltage-dependent sodium
channels, and 3) ability to interfere with intracellular events that
follow transmitter binding at excitatory amino acid receptors. |
Absorption |
Riluzole is well-absorbed (approximately 90%), with average
absolute oral bioavailability of about 60% (CV=30%). A high fat meal
decreases absorption, reducing AUC by about 20% and peak blood levels by
about 45%. |
Volume of distribution |
Not Available |
Protein binding |
96% bound to plasma proteins, mainly to albumin and lipoprotein over the clinical concentration range. |
Metabolism |
Riluzole is extensively metabolized to six major and a number of
minor metabolites, which have not all been identified to date.
Metabolism is mostly hepatic, consisting of cytochrome P450–dependent
hydroxylation and glucuronidation. CYP1A2 is the primary isozyme
involved in N-hydroxylation; CYP2D6, CYP2C19, CYP3A4, and CYP2E1 are
considered unlikely to contribute significantly to riluzole metabolism
in humans. |
Route of elimination |
Not Available |
Half life |
The mean elimination half-life of riluzole is 12 hours (CV=35%) after repeated doses. |
Clearance |
Not Available |
Toxicity |
Not Available |
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