Baclofen may inhibit the transmission of impulses through these pathways by acting as an inhibitory neurotransmitter itself or by hyperpolarizing the primary afferent nerve terminals, which inhibits the release of excitatory neurotransmitters such as glutamate and aspartic acids. Because large doses of baclofen cause CNS depression, it is postulated that the drug works at supraspinal sites as well. Both the rate and extent of absorption is inversely proportional to the dose. Peak blood concentrations are achieved within 2-3 hours. Baclofen is distributed throughout the body but only minimally crosses the blood-brain barrier.
Protein binding is low.
Patients with renal impairment may require a reduced dose of baclofen to avoid drug accumulation. In addition, elderly patients or patients with pre-existing psychiatric disorders may be more susceptible to baclofen's CNS toxicities. Baclofen can increase blood glucose concentrations, so it should be used cautiously in patients with diabetes mellitus. Baclofen has caused deterioration in seizure control and EEG changes in patients with epilepsy. Baclofen should be prescribed cautiously to patients with a history of a seizure disorder.