| Indication |
For the alleviation of signs and symptoms of spasticity resulting
from multiple sclerosis, particularly for the relief of flexor spasms
and concomitant pain, clonus, and muscular rigidity. |
| Pharmacodynamics |
Baclofen is a muscle relaxant and antispastic. Baclofen is
useful for the alleviation of signs and symptoms of spasticity resulting
from multiple sclerosis, particularly for the relief of flexor spasms
and concomitant pain, clonus, and muscular rigidity. Although Baclofen
is an analog of the putative inhibitory neurotransmitter
gamma-aminobutyric acid (GABA), there is no conclusive evidence that
actions on GABA systems are involved in the production of its clinical
effects. In studies with animals, Baclofen has been shown to have
general CNS depressant properties as indicated by the production of
sedation with tolerance, somnolence, ataxia, and respiratory and
cardiovascular depression. Baclofen is rapidly and extensively absorbed
and eliminated. Absorption may be dose-dependent, being reduced with
increasing doses. Baclofen is excreted primarily by the kidney in
unchanged form and there is relatively large intersubject variation in
absorption and/or elimination. |
| Mechanism of action |
Baclofen is a direct agonist at GABAB receptors. The precise
mechanism of action of Baclofen is not fully known. It is capable of
inhibiting both monosynaptic and polysynaptic reflexes at the spinal
level, possibly by hyperpolarization of afferent terminals, although
actions at supraspinal sites may also occur and contribute to its
clinical effect. |
| Absorption |
Rapidly and almost completely absorbed from the GI tract. |
| Volume of distribution |
|
| Protein binding |
30% |
| Metabolism |
~ 15% of the dose is metabolized in the liver, primarily by
deamination. 70-80% of the dose is excreted unchanged or as metabolites
in urine and the remainder is excreted in feces. |
| Route of elimination |
In a study using radiolabeled baclofen, approximately 85% of the
dose was excreted unchanged in the urine and feces.
Baclofen is excreted primarily by the kidney as unchanged drug; 70 - 80%
of a dose appears in the urine as unchanged drug. The remainder is
excreted as unchanged drug in the feces or as metabolites in the urine
and feces. |
| Half life |
2.5-4 hours |
| Clearance |
|
| Toxicity |
LD50=45 mg/kg (male mice, IV); LD50=78 mg/kg (male rat, IV) |
