A comparative study on pharmacokinetics and tissue distribution of 5-hydroxy-4-methoxycanthin-6-one and its metabolite in normal and dextran sodium sulfate-induced colitis rats by HPLC-MS/MS

Abstract

Objectives This study aimed to investigate the existing form of 5-hydroxy-4methoxycanthin-6-one (PQ-A) in vivo after oral administration and the effects on its pharmacokinetics and tissue distribution by colitis. Methods A rapid HPLC-MS/MS method was established to simultaneously determine PQ-A and its main metabolite, 1-methoxicabony-b-carboline (PQ-B), in biological samples acquired from normal and dextran sodium sulfate (DSS)induced colitic rats administered orally with PQ-A. Then, the pharmacokinetics of both PQ-A and PQ-B, and tissue distribution of PQ-A in the above two states were analysed. Key findings The pharmacokinetic results showed that the prototype of PQ-A was the main existing form in both physiological and pathological conditions. And significant difference between the above two status in pharmacokinetics of PQ-A was observed, such as higher exposure and longer elimination in colitis than that in normal rats. It suggested that the pharmacokinetics of medications for colitis was affected by enteritis. The tissue distribution studies displayed that PQ-A mainly accumulated in intestinal tract. Especially, the distribution of PQ-A in intestinal tract was increased obviously in colitic rats. Conclusions These results contributed to further illuminate the ADME process of PQ-A in different status and were prospected to be the reference to the clinical application of similar medicines in pathological states. Consequently, the pathological changes in enteritis may be associated with changes in all phases of pharmacokinetic processes, including absorption, distribution, metabolism and excretion (ADME). Accessing to the previous research, other similar studies have adequately demonstrated the differences in pharmacokinetics under physiological and pathological conditions. Research shows that diabetes, liver injury, inflammation, cerebral ischaemia and other diseases could alter the drug's metabolism. [5] For example, it is reported that the pharmacokinetic characteristics of phlorizin were significantly changed in type 2 diabetes colitic rats, especially the bioavailability was significantly higher than that in normal rats. [6] It suggested that the pharmacokinetics of drugs is influenced by the internal environment when organisms are

Pharmacokinetic Study of Four Major Bioactive Components of Liandan Xiaoyan Formula in Ulcerative Colitis and Control Rats Using UPLC-MS/MS

“…Andrographolide (Lot number 110797-201609) and dehydroandrographolide (Lot number 110854-201710) were purchased from National Institutes for Food and Drug Control (Beijing, China). 1-methoxicabony-β-carboline and 4-methoxy-5-hydroxy-canthin-6-one were purified and identified using Infrared Spectroscopy (IR), UV–visible spectroscopy (UV), mass spectrometry (MS), and Nuclear Magnetic Resonance Spectroscopy (NMR) as described in our previous studies, and the purity of them was more than 98% ( Yang et al, 2016 ; Liu et al, 2020 ; Zhang et al, 2021 ). Chloramphenicol (Lot number Y27M6C2), internal standard (IS), was purchased from Shanghai Yuanye Bio-Technology Co., Ltd (Shanghai, China).…”

“…These days, ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole/time of flight mass spectrometry (UPLC-MS/MS) has been used as a general approach for metabolic and pharmacokinetic profiling study of natural products ( Yao et al, 2018 ; Li et al, 2019 ; Wu et al, 2020 ). Recent research has also shown that the internal environment could influence the pharmacokinetics of drugs in a pathological state, such as colitis ( Liu et al, 2020 ). It is indicated that pharmacokinetic study of XLF in UC state is necessary to provide a basis for clinical use.…”

Nigakinone alleviates DSS‐induced experimental colitis via regulating bile acid profile and FXR/NLRP3 signaling pathways

“…Nigakinone (5-hydroxy-4-methoxycanthin-6-one) is the main effective component of Ramulus et Folium Picrasmae, a commonly used traditional Chinese medicine for the treatment of dysentery, colitis, and gastroenteritis (Liu et al, 2020). Pharmacological researches have proven that nigakinone possesses anti-inflammatory, anti-bacterial, and cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitory activities (Gong et al, 2018), and ameliorating effects on DSS-induced colitic rats.…”

In-depth comparison of the metabolic and pharmacokinetic behaviour of the structurally related synthetic cannabinoids AMB-FUBINACA and AMB-CHMICA in rats

“…In intoxication cases, the pharmacokinetics and excretion of these metabolites cannot be fully evaluated in many cases, because of the first sampling is performed during clinical cares after intoxication diagnosis. At this point, in vivo experiments in model animals provide information about the metabolism of a certain substance, as well as the distribution of the parent compound and/or metabolites in different tissues along the time, including the excretion of these compounds 25 .…”