Lasmiditan undergoes hepatic and extrahepatic metabolism primarily by non-CYP enzymes.1

Lasmiditan is primarily eliminated via metabolism. Major metabolites of lasmiditan identified in plasma and urine are

• S-M8, through ketone reduction to the alcohol (major pathway), 
• M7, through oxidation on piperidine ring, and
• M18, through a combination of M7 and M8 pathways.1

Relative to lasmiditan, these metabolites exhibited considerably lower affinity (~1000-fold lower K_i) for the target 5-HT_1F receptor and are considered pharmacologically inactive.1

The following enzymes are not involved in metabolism of lasmiditan, including

• MAO-A
• MAO-B
• flavin monooxygenase 3
• CYP450 reductase
• xanthine oxidase
• alcohol dehydrogenase 
• aldehyde dehydrogenase, and
• aldo-keto reductases.1

Renal excretion is a minor route of lasmiditan clearance with approximately 3% of the dose recovered as unchanged lasmiditan in urine. Metabolite S-M8 represented approximately 66% of the dose in urine, with the majority of recovery within 48 hours post-dose.1