Metabolism of Speciociliatine, an Overlooked Kratom Alkaloid for its Potential Pharmacological Effects

In this report, we have characterized the metabolism of speciociliatine in human and preclinical sp ecies (mouse, rat, dog, and cynomolgus monkey) liver microsomes and hepatocytes. Speciociliatine metabolized rapidly in monkey, rat, and mouse hepatocytes (in vitro half-life was 6.6 ± 0.2, 8.3 ± 1.1, 11.2 ± 0.7 min, respectively), while a slower metabolism was observed in human and dog hepatocytes (91.7 ± 12.8 and >  120 min, respectively). Speciociliatine underwent extensive metabolism, primarily through monooxidation andO-demethylation metabolic pathways in liver microsomes and hepatocytes across species. No human-specific or disproportionate metabolites of speciociliatine were found in human liver microsomes. The metabolism of speciociliatine was predominantly mediated by CYP3A4 with minor contributions by CYP2D6.
Source: The AAPS Journal - Category: Drugs & Pharmacology Source Type: research