N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Acad. Lavrentiev Ave., 9, Novosibirsk, 630090, Russia; Novosibirsk State University, Pirogov Str., 2, Novosibirsk, 630090, Russia.
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Acad. Lavrentiev Ave., 9, Novosibirsk, 630090, Russia; Novosibirsk State University, Pirogov Str., 2, Novosibirsk, 630090, Russia.
J Pharm Biomed Anal. 2018 Nov 30;161:383-392. doi: 10.1016/j.jpba.2018.09.003. Epub 2018 Sep 5.
Major metabolites of camphecene, a new effective antiviral agent, formed after its oral administration to rats and excreted in the urine, were found and identified using liquid chromatography coupled to mass spectrometry as well as multivariate analysis of HPLC-MS data. The metabolites were found to be camphecene glucuronide, camphecene sulfate and the corresponding iminoacid. A study of the dynamics of accumulation of camphecene and its metabolites in the liver, kidneys, lungs and brain of animals was performed. Maximum concentration of camphecene in blood and organs was reached after 1.5-2 h of its administration, and the maximal content of the agent in the organs investigated was observed in the kidneys. The content of the substance in the lungs was comparable to that in the liver. Also, camphecene was found in brain in high concentration, thus allowing assumption of its ability to penetrate the blood-brain barrier and to exert its antiviral properties in the organ. Camphecene glucuronide and iminoacid had concentration-time profiles similar to that of their precursor, their content being maximal in kidney and liver and 2-3 orders of magnitude higher than in lungs and brain. The content of camphecene sulfate was of similar level in all organs studied. The results obtained made it possible to develop recommendations for therapy with the use of camphecene.
新型有效抗病毒剂莰烯经大鼠口服给药后的主要代谢物及其在尿液中的排泄物被发现,并通过液相色谱-质谱联用和 HPLC-MS 数据的多变量分析鉴定。代谢物被鉴定为莰烯葡萄糖醛酸苷、莰烯硫酸盐和相应的亚氨基酸。研究了莰烯及其代谢物在动物肝脏、肾脏、肺和脑中的积累动力学。莰烯及其代谢物在给药后 1.5-2 小时达到血液和器官中的最大浓度,在所研究的器官中观察到该药物的最大含量在肾脏中。该物质在肺部的含量与在肝脏中的含量相当。此外,莰烯在大脑中以高浓度存在,这使得可以假设它能够穿透血脑屏障并在该器官中发挥其抗病毒特性。莰烯葡萄糖醛酸苷和亚氨基酸的浓度-时间曲线与它们的前体相似,其在肾脏和肝脏中的含量最高,比在肺和脑中高 2-3 个数量级。在所研究的所有器官中,莰烯硫酸盐的含量水平相似。所得结果使得能够制定使用莰烯进行治疗的建议。