In a study using dogs, the combination of infusing riluzole directly into the spinal cord and also taking it orally increased the concentration of the medication in the spinal cord significantly, compared to oral administration alone.
The results of the study suggest that this combination therapy may increase its benefits in the treatment of amyotrophic lateral sclerosis (ALS) without increasing the risk of adverse side effects.
The study, “Intrathecal Riluzole for the Treatment of Patients With Amyotrophic Lateral Sclerosis,” was published recently in the journal Neurosurgery. It also is scheduled to be presented in October at the 2019 Congress of Neurological Surgeons Annual Meeting in San Francisco.
Riluzole (brand name Rilutek when dispensed in tablets, and Tiglutik when dispensed as oral liquid) is the first treatment approved by the U.S. Food and Drug Administration (FDA) that is known to help improve the survival of ALS patients.
Studies have demonstrated that oral riluzole has modest effectiveness and the dose at which it is administered is limited by hepatic (liver) toxicity and asthenia (abnormal physical weakness or lack of energy).
When administered orally, the amount of riluzole that actually reaches the nerve cells for which it is intended is decreased.
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So, researchers sought to determine if continuous intrathecal (IT) delivery (infused directly into the spinal fluid) of low daily doses of riluzole could increase concentration of the drug in the spinal cord well above those that are achievable with oral treatment alone, without increasing the side effects.
Researchers used purpose-bred hound dogs that were administered oral riluzole in combination with one of three IT doses that were given through continuous infusion.
Then, the concentration of riluzole in the blood, spinal cord and brain were measured, along with an assessment of safety and tolerability.
Researchers conducted the assessments at two time points, six weeks and 24 weeks post-treatment.
Results from the six-week study showed that when oral and IT delivery methods were combined, there was a significant increase in the concentration of the drug in the spinal cord, compared to what would have been achieved through oral riluzole alone.
Additionally, researchers found that all three IT doses in combination with oral riluzole were well-tolerated by the animals.
Results from the six-month study, in which the lowest dose from the six-week study was dropped and a higher dose was added, showed that the highest dose of IT riluzole was not well-tolerated by the dogs.
The authors concluded that continuous IT administration of riluzole — when combined with oral administration — increases the concentration of the drug in the spinal cord significantly more than is achievable by oral therapy alone.
Importantly, this increase in drug concentration occurs without increasing the risk for adverse side effects that are associated with constant drug exposure or off-target side effects in the brain.
The researchers added that the combined riluzole therapy may safely enhance neuroprotection and boost the drug’s benefits through improved delivery into the spinal cord. “With a careful selection of IT doses, it could be implemented in patients with ALS,” they wrote.