It is also neuroprotective in various in vivo experimental models of neuronal injury involving excitotoxic mechanisms. In in vitro tests, riluzole protected cultured rat motor neurons from the excitotoxic effects of glutamic acid and prevented the death of cortical neurons induced by anoxia. Pharmacokinetics are linear over a dose range of 25-100 mg given every 12 hours. Both tablets have been used in clinical trials. Metabolism and Elimination Riluzole is extensively metabolized to six major and a number of minor metabolites, not all of which have been identified.
Some metabolites appear pharmacologically active in in vitro assays.
The metabolism of riluzole is mostly hepatic and consists of cytochrome P450-dependent hydroxylation and glucuronidation. In vitro studies using liver microsomes wshow that hydroxylation of the primary amine group producing N-hydroxyriluzole is the main metabolic pathway in human, monkey, dog and rabbit. In humans, cytochrome P450 1A2 is the principal isozyme involved in N-hydroxytation. In vitro studies predict that CYP2D6, CYP 2C19, CYP 3A4 and CYP 2E1 are unlikely to contribute significantly to riluzole metabolism in humans. CYP 1A2 activity has been reported to be lower in women than in men.