Speciociliatine Metabolism and Drug Interaction

Bar chart of hepatocyte t½ by species

Bar chart of hepatocyte t½ by species

Hepatocyte t½ (min)

Hepatocyte t½ (min)

Pathways & enzymes

  • Dominant biotransformations: O-demethylation of the 9-methoxyindole and multiple mono-oxidations on the indoloquinolizine scaffold; no human-specific/disproportionate metabolites in HLM.
  • Enzymology: CYP3A4 is the predominant enzyme; CYP2D6 contributes minimally (recombinant phenotyping; inhibition tools).

    • Hepatocyte intrinsic stability (1 μM)

    Mouse ~11.2 min; Rat ~8.3 min; Cynomolgus ~6.6 min; Dog >120 min; Human ~91.7 min — indicating species differences (notably slow turnover in human and dog).

    What this means for DDI copy

  • Given CYP3A4 predominance, warn readers that strong CYP3A modulators (inhibitors/inducers) could alter exposure; emphasize the absence of clinical DDI trials specific to speciociliatine to date. (Mechanistic inference from phenotyping.)