Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA.
Translational Drug Development Core, Clinical and Translational Sciences Institute, University of Florida, Gainesville, FL, 32610, USA.
AAPS J. 2022 Jul 19;24(5):86. doi: 10.1208/s12248-022-00736-8.
Speciociliatine, a diastereomer of mitragynine, is an indole-based alkaloid found in kratom (Mitragyna speciosa). Kratom has been widely used for the mitigation of pain and opioid dependence, as a mood enhancer, and/or as an energy booster. Speciociliatine is a partial µ-opioid agonist with a 3-fold higher binding affinity than mitragynine. Speciociliatine has been found to be a major circulating alkaloid in humans following oral administration of a kratom product. In this report, we have characterized the metabolism of speciociliatine in human and preclinical species (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 and O-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.
别育孕草碱是一种异坎根碱，存在于咔特（Mitragyna speciosa）中，是一种吲哚基生物碱。咔特被广泛用于缓解疼痛和阿片类药物依赖，作为一种情绪增强剂，和/或作为一种能量助推器。别育孕草碱是一种部分μ-阿片受体激动剂，与米那若碱的结合亲和力高 3 倍。在人类口服咔特产品后，别育孕草碱已被发现是主要的循环生物碱。在本报告中，我们对别育孕草碱在人类和临床前物种（小鼠、大鼠、狗和食蟹猴）肝微粒体和肝细胞中的代谢进行了特征描述。别育孕草碱在猴、大鼠和小鼠肝细胞中快速代谢（体外半衰期分别为 6.6±0.2、8.3±1.1 和 11.2±0.7 min），而在人源和犬源肝细胞中观察到代谢较慢（分别为 91.7±12.8 和>120 min）。别育孕草碱经历了广泛的代谢，主要通过肝微粒体和肝细胞中的单氧化和 O-去甲基化代谢途径在各种物种中进行。在人源肝微粒体中未发现别育孕草碱的人类特异性或不成比例的代谢物。别育孕草碱的代谢主要由 CYP3A4 介导，CYP2D6 也有少量贡献。
