Metabolites profiling and pharmacokinetics of troxipide and its pharmacodynamics in rats with gastric ulcer. 2020

Hongbin Guo, and Baohua Chen, and Zihan Yan, and Jian Gao, and Jiamei Tang, and Chengyan Zhou
College of Pharmaceutical Sciences, Institute of Life Science and Green Development, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, 180 WuSi Road, Lianchi District, Baoding, 071002, China.

Troxipide is widely used to treat gastric ulcer (GU) in the clinic. However, a lack of systematic metabolic, pharmacokinetic and pharmacological studies limits its clinical use. This study aimed to firstly explore the metabolic, pharmacokinetic and pharmacological mechanisms of troxipide in rats with GU compared to normal control (NC) rats. First, metabolic study was perormed by a highly selective, high-resolution mass spectrometry method. A total of 45 metabolites, including 9 phase I metabolites and 36 phase II metabolites, were identified based on MS/MS spectra. Subsequently, the pharmacokinetics results suggested that the Cmax, Ka, t1/2, AUC(0-t) and AUC(0-∞) of troxipide were significantly increased in rats with GU compared with NC rats. The Vz, K10 and absolute bioavailability of troxipide were obviously decreased in rats with GU compared with NC rats, and its tissue distribution (in the liver, lung and kidney) was significantly different between the two groups of rats. Additionally, the pharmacodynamic results suggested that the levels of biochemical factors (IL-17, IL-6, TNF-α, IFN-γ, AP-1, MTL, GAS, and PG-II) were significantly increased, the PG-Ӏ level was obviously decreased, and the protein expression levels of HSP-90, C-Cas-3 and C-PARP-1 were markedly increased in rats with GU compared with NC rats. The above results suggested that the therapeutic mechanisms underlying the metabolic, pharmacokinetic and pharmacological properties of troxipide in vivo in rats deserve further attention based on the importance of troxipide in the treatment of GU in this study, and these mechanisms could be targets for future studies.

UI MeSH Term Description Entries
D008297 Male Males
D010880 Piperidines A family of hexahydropyridines.
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001682 Biological Availability The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action. Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities
D013276 Stomach Ulcer Ulceration of the GASTRIC MUCOSA due to contact with GASTRIC JUICE. It is often associated with HELICOBACTER PYLORI infection or consumption of nonsteroidal anti-inflammatory drugs (NSAIDS). Gastric Ulcer,Gastric Ulcers,Stomach Ulcers,Ulcer, Gastric,Ulcer, Stomach,Ulcers, Gastric,Ulcers, Stomach
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions
D015415 Biomarkers Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc. Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune
D016022 Case-Control Studies Comparisons that start with the identification of persons with the disease or outcome of interest and a control (comparison, referent) group without the disease or outcome of interest. The relationship of an attribute is examined by comparing both groups with regard to the frequency or levels of outcome over time. Case-Base Studies,Case-Comparison Studies,Case-Referent Studies,Matched Case-Control Studies,Nested Case-Control Studies,Case Control Studies,Case-Compeer Studies,Case-Referrent Studies,Case Base Studies,Case Comparison Studies,Case Control Study,Case Referent Studies,Case Referrent Studies,Case-Comparison Study,Case-Control Studies, Matched,Case-Control Studies, Nested,Case-Control Study,Case-Control Study, Matched,Case-Control Study, Nested,Case-Referent Study,Case-Referrent Study,Matched Case Control Studies,Matched Case-Control Study,Nested Case Control Studies,Nested Case-Control Study,Studies, Case Control,Studies, Case-Base,Studies, Case-Comparison,Studies, Case-Compeer,Studies, Case-Control,Studies, Case-Referent,Studies, Case-Referrent,Studies, Matched Case-Control,Studies, Nested Case-Control,Study, Case Control,Study, Case-Comparison,Study, Case-Control,Study, Case-Referent,Study, Case-Referrent,Study, Matched Case-Control,Study, Nested Case-Control

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