Current drug metabolism最新文献

{"title":"The Impact of Certain Pharmacogenetic Differences on the Metabolism of Antiretroviral Drugs Used in A Black South African Population.","authors":"Riaan Reay, Michelle Viljoen, Malie Rheeders","doi":"10.2174/0113892002255240231117072211","DOIUrl":"10.2174/0113892002255240231117072211","url":null,"abstract":"<p><strong>Background: </strong>Genetic polymorphism of drug-metabolising enzymes and transporters may influence the effect and toxicity of antiretroviral drugs.</p><p><strong>Objectives: </strong>To determine and compare the minimum allele frequency of 20 single nucleotide polymorphisms (SNPs) with possible involvement in the metabolism of the antiretroviral drugs with other populations. To investigate the influence of these variants on Reverse transcriptase, Protease and Integrase strand transfer inhibitor drugs.</p><p><strong>Method: </strong>DNA samples were collected from 1489 subjects. All SNPs with a gene call score of > 0.6 were selected for genotyping. The R package calculated call rates, MAF and Hardy-Weinberg equilibrium (HWE), test p-values, and Chi-squared analysis were performed on the data. The Fisher's exact test compared the allele frequencies between the populations.</p><p><strong>Results: </strong>The highest similarities in minimum allele frequency (MAF) were between the Prospective Urban and Rural Epidemiological group (PURE), a Black population in South Africa, and the Yoruba and Luhya populations in Africa. The following SNPs were identified with a possible effect on metabolism: CYP2B6 rs28399494 (MAF 11%) is indicated in the toxicity of Efavirenz and Nevirapine. CYP3A5 rs776746 (MAF 17%) and CYP3A4 rs2749674 (MAF 23%) both cause an increase in the metabolism of the protease inhibitors. The very low MAF values for both SCL01B1 rs4149056 (MAF 0.6%) and ABCC rs717620 (MAF 2.8%) are indications that OATP1B1 transport function and glomerular filtration tempo will not be compromised. The high MAF value of 30% for UGTA1 rs10929302 can result in hyperbilirubinemia, which can decrease the clearance of Dolutegravir.</p><p><strong>Conclusion: </strong>These results show a possibility of kidney protection and an increase in bilirubin in this population.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Framework Nucleic Acids: A Promising Vehicle for Small Molecular Cargos.","authors":"Junjiang Zhang,&nbsp;Jiayin Li,&nbsp;Lei Sui,&nbsp;Yanjing Li","doi":"10.2174/1389200224666230120124402","DOIUrl":"10.2174/1389200224666230120124402","url":null,"abstract":"<p><p>Framework nucleic acids (FNAs), which are a series of self-assembled DNA nanostructures, are highly versatile tools for engineering intelligent molecular delivery vehicles. Owing to their precise and controllable design and construction, excellent programmability and functionality, as well as favorable intercalation between DNA and small molecules, FNAs provide a promising approach for small molecule delivery. This review discusses the advantages, applications, and current challenges of FNAs for the delivery of small molecular cargo. First, the physicochemical and biological properties that make FNAs favorable for the transport of small molecules are introduced. Thereafter, the classification of loaded cargos and the mechanism of combination between small molecules and FNAs are summarized in detail, and recent research on FNA-based delivery systems and their applications are highlighted. Finally, the challenges and prospects of FNA nanocarriers are discussed to advance their exploitation and clinical adoption.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10564412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In vivo</i> Metabolism of Nifurtimox and the Drug-Drug Interaction Potential Including its Major Metabolites.","authors":"Simone I Schulz, Dieter Lang, Gabriele Schmuck, Michael Gerisch, Michaela Bairlein, Robert Fricke, Heino Stass","doi":"10.2174/1389200224666230817114758","DOIUrl":"10.2174/1389200224666230817114758","url":null,"abstract":"<p><strong>Background: </strong>Nifurtimox is an effective treatment for patients with Chagas disease, but knowledge of its biotransformation and excretion is limited.</p><p><strong>Objective: </strong>This study aimed to better understand the fate of oral nifurtimox <i>in vivo</i>.</p><p><strong>Methods: </strong>We investigated the exposure and excretion pathways of [¹⁴C]-labeled nifurtimox and its metabolites in rats. We then quantified the prominent metabolites and nifurtimox in the urine and plasma of patients receiving nifurtimox using LC-HRMS with reference standards and quantified these compounds in rat plasma after a single, high dose of nifurtimox. We also investigated potential drug-drug interactions (DDIs) of these compounds <i>in vitro</i>.</p><p><strong>Results: </strong>In rats, orally administered nifurtimox was rapidly absorbed (t_max 0.5 h) and eliminated (t_½ 1.4 h). Metabolism of nifurtimox yielded six predominant metabolites (M-1 to M-6) in urine and plasma, and the dose was excreted equally via the renal and fecal routes with only traces of unchanged nifurtimox detectable due to its instability in excreta. In patients with Chagas disease, only M-6 and M-4 achieved relevant exposure levels, and the total amount of excreted metabolites in urine was higher in fed <i>versus</i> fasted patients, consistent with the higher systemic exposure. For nifurtimox, M-6, and M-4, no potential perpetrator pharmacokinetic DDIs with the main cytochrome P- 450 enzymes and drug transporters were identified <i>in vitro</i>.</p><p><strong>Conclusion: </strong>This contemporary analysis of the complex metabolite profile and associated exposures emerging after oral dosing of nifurtimox in rats and humans, together with the expected low risk for clinically relevant DDIs, expands the understanding of this important anti-trypanosomal drug.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10661964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10018705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global Xenobiotic Profiling of Rat Plasma Using Untargeted Metabolomics and Background Subtraction-Based Approaches: Method Evaluation and Comparison.","authors":"Xiaojuan Jiang,&nbsp;Simian Chen,&nbsp;Mingshe Zhu,&nbsp;Caisheng Wu","doi":"10.2174/1389200224666230508122240","DOIUrl":"https://doi.org/10.2174/1389200224666230508122240","url":null,"abstract":"<p><strong>Background: </strong>Global xenobiotic profiling (GXP) is to detect and structurally characterize all xenobiotics in biological samples using mainly liquid chromatography-high resolution mass spectrometry (LC-HRMS) based methods. GXP is highly needed in drug metabolism study, food safety testing, forensic chemical analysis, and exposome research. For detecting known or predictable xenobiotics, targeted LC-HRMS data processing methods based on molecular weights, mass defects and fragmentations of analytes are routinely employed. For profiling unknown xenobiotics, untargeted and LC-HRMS based metabolomics and background subtraction-based approaches are required.</p><p><strong>Objective: </strong>This study aimed to evaluate the effectiveness of untargeted metabolomics and the precise and thorough background subtraction (PATBS) in GXP of rat plasma.</p><p><strong>Methods: </strong>Rat plasma samples collected from an oral administration of nefazodone (NEF) or <i>Glycyrrhizae Radix et Rhizoma</i> (Gancao, GC) were analyzed by LC-HRMS. NEF metabolites and GC components in rat plasma were thoroughly searched and characterized <i>via</i> processing LC-HRMS datasets using targeted and untargeted methods.</p><p><strong>Results: </strong>PATBS detected 68 NEF metabolites and 63 GC components, while the metabolomic approach (MS-DIAL) found 67 NEF metabolites and 60 GC components in rat plasma. The two methods found 79 NEF metabolites and 80 GC components with 96% and 91% successful rates, respectively.</p><p><strong>Conclusion: </strong>Metabolomics methods are capable of GXP and measuring alternations of endogenous metabolites in a group of biological samples, while PATBS is more suited for sensitive GXP of a single biological sample. A combination of metabolomics and PATBS approaches can generate better results in the untargeted profiling of unknown xenobiotics.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10096671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Intracellular Metabolism of Methotrexate in Hepatocytes and Embryonic Kidney Cells based on Folylpolyglutamate Synthetase and Gamma-Glutamyl Hydrolase Expression.","authors":"Hanbing Jiang,&nbsp;Jie Yang,&nbsp;Yucui Hou,&nbsp;Ke Zhang,&nbsp;Yi Ren,&nbsp;Jing Huang,&nbsp;Huanhuan Li,&nbsp;Tongji Cai,&nbsp;Zhonghua Ouyang,&nbsp;Jia Zhao,&nbsp;Peng Yu","doi":"10.2174/1389200224666230406120714","DOIUrl":"https://doi.org/10.2174/1389200224666230406120714","url":null,"abstract":"<p><strong>Background: </strong>Methotrexate (MTX) is a common folic acid antagonist in clinical medicine, easily inducing a common adverse side effect of liver and kidney injury. It has been found that the expression of Folylpolyglutamate Synthetase (FPGS) and gamma-Glutamyl Hydrolase (GGH) may be closely related to that of related proteins to affect the intracellular metabolism of MTX.</p><p><strong>Objective: </strong>The relationship between FPGS/GGH and MTXPGs accumulation in liver and kidney cells was explored by adjusting the expression of FPGS and GGH in cells using UPLC-MS/MS quantitative technology.</p><p><strong>Method: </strong>Based on UPLC-MS/MS quantitative techniques, the relationship between MTXPGs accumulation and FPGS/GGH in hepatocytes and embryonic kidney cells was explored by adjusting the expression of FPGS and GGH, and the effect of FPGS/GGH on the intracellular toxicity of MTX was comprehensively analyzed.</p><p><strong>Result: </strong>The results showed that the difference in methotrexate polyglutamates (MTXPGs) accumulation in liver and kidney cells was related to the difference in FPGS and GGH expression. The expression of FPGS interacted with that of GGH. These results suggest that the protein abundance ratio of FPGS to GGH (FPGS/GGH) has more potential to be used as a predictor of MTX efficacy than the FPGS or GGH single protein index. This can effectively avoid liver and kidney damage caused by MTX and guides the rational use of drugs in MTX.</p><p><strong>Conclusion: </strong>The results prove that there is a positive correlation between the FPGS/GGH and the accumulation of MTXPGS in liver and kidney cells. Summarily, the FPGS/GGH is expected to be a predictor for MTXPGs accumulation and provides an effective method to evaluate the toxicity caused by MTX.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9551054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated 16S rRNA Sequencing and Untargeted Metabolomics Analysis to Reveal the Protective Mechanisms of <i>Polygonatum sibiricum</i> Polysaccharide on Type 2 Diabetes Mellitus Model Rats.","authors":"Hui Zhang,&nbsp;Hanzhou Li,&nbsp;Baochao Pan,&nbsp;Shufang Zhang,&nbsp;Xiuhai Su,&nbsp;Wenjuan Sun,&nbsp;Tianyu Zhang,&nbsp;Zhaiyi Zhang,&nbsp;Shuquan Lv,&nbsp;Huantian Cui","doi":"10.2174/1389200224666230406114012","DOIUrl":"https://doi.org/10.2174/1389200224666230406114012","url":null,"abstract":"<p><strong>Background: </strong><i>Polygonatum sibiricum</i> polysaccharide (PSP) can improve insulin resistance and inhibit oxidative stress. However, the detailed anti-diabetic mechanism of PSP is still poorly defined.</p><p><strong>Methods: </strong>In this study, the anti-diabetic, anti-inflammatory and anti-oxidative effects of PSP were evaluated on a type 2 diabetes mellitus (T2DM) rat model. Furthermore, we investigated the changes in gut microbiota and serum metabolites in T2DM rats after PSP treatment through 16S rRNA sequencing and untargeted metabolomics analyses.</p><p><strong>Results: </strong>Our results showed that PSP exhibited significant anti-diabetic, anti-inflammatory and anti-oxidative effects on T2DM model rats. In addition, 16S rRNA sequencing showed that PSP treatment decreased the <i>Firmicutes/ Bacteroidetes</i> ratio in the gut. At the genus level, PSP treatment increased the relative abundances of <i>Blautia, Adlercreutzia, Akkermansia</i> and <i>Parabacteroides</i> while decreasing <i>Prevotella, Megamonas funiformis</i> and <i>Escherichia</i>. Untargeted metabolomics analysis revealed that PSP treatment could affect 20 metabolites, including hexanoylglycine, (±)5(6)-DiHET, ecgonine, L-cysteine-S-sulfate, epitestosterone, (±)12(13)-DiHOME, glutathione, L-ornithine, Dmannose 6-phosphate, L-fucose, L-tryptophan, L-kynurenine, serotonin, melatonin, 3-hydroxyanthranilic acid, xylitol, UDP-D-glucuronate, hydroxyproline, 4-guanidinobutyric acid, D-proline in T2DM model rats, these metabolites are associated with arginine and proline metabolism, tryptophan metabolism, amino sugar and nucleotide sugar metabolism, pentose and glucuronate interconversions, glutathione metabolism, arginine biosynthesis, ascorbate and aldarate metabolism pathways. Spearman correlation analysis results showed that the modulatory effects of PSP on the arginine and proline metabolism, tryptophan metabolism, and glutathione metabolism pathways were related to the regulation of <i>Prevotella, Megamonas funiformis, Escherichia, Blautia</i> and <i>Adlercreutzia</i>.</p><p><strong>Conclusion: </strong>Our research revealed the therapeutic, anti-inflammatory and anti-oxidative effects of PSP on T2DM. The mechanisms of PSP on T2DM are associated with improving the dysbiosis of gut microbiota and regulating arginine and proline metabolism, tryptophan metabolism, and glutathione metabolism in serum.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10101416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Influencing ADME Properties Of Drugs: Advances and Applications (Part II).","authors":"Shuang-Qing Zhang,&nbsp;Feng Chen","doi":"10.2174/138920022407230928104259","DOIUrl":"10.2174/138920022407230928104259","url":null,"abstract":"","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49689145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Pharmacokinetic Interplay of Atorvastatin on Lacosamide and Levetiracetam on Experimental Convulsions in Mice.","authors":"Jayaraman Rajangam, Arun Prasath Lakshmanan, Narahari N Palei, Karthikeyan Elumalai, Muddukrishnaiah Kotakonda, R Prakash, P Latha","doi":"10.2174/0113892002253895231020100743","DOIUrl":"10.2174/0113892002253895231020100743","url":null,"abstract":"<p><strong>Background: </strong>The beneficial effects of statins, other than their hypocholesterolemia role, have been well documented, however, their use as an adjuvant drug with other antiseizure drugs, in the treatment of epilepsy is poorly understood.</p><p><strong>Objective: </strong>This study aimed to investigate the symbiotic effect of ATOR along with either lacosamide (LACO) or levetiracetam (LEVE) on experimentally induced epilepsy (Maximal electro-shock-MES or pentylenetetrazol- PTZ) in mice models.</p><p><strong>Methods: </strong>Conventional elevated-maze (EPM) and rotarod methods were performed to observe the behavioral effects.</p><p><strong>Results: </strong>In both the animal models, we found that co-administration of ATOR along with LACO showed a significant reduction in hind-limb extension (HLE) and clonic convulsion (CC) responses, respectively, but not in the ATOR+LEVE treated group. Intriguingly, comparable Straub tail response and myoclonic convulsion as the diazepam (DIA) group were observed only in the ATOR+LACO treated group. Moreover, a significant muscle-grip strength was observed in both groups. Also, pharmacokinetic analysis has indicated that the mean plasma concentration of ATOR peaked at 2nd hr in the presence of LACO but marginally peaked in the presence of LEVE. An Insilico study has revealed that ATOR has a higher binding affinity toward neuronal sodium channels.</p><p><strong>Conclusion: </strong>This study has demonstrated that the plasma concentration of ATOR was potentiated in the presence of LACO, but not in the presence of LEVE and it has provided significant protection against both the electro and chemo-convulsive models in mice. This could be due to the symbiotic pharmacokinetic interplay of ATOR with LACO, and possibly, this interplay may interfere with sodium channel conductance.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Which can Predict the Outcome of Antidepressants: Metabolic Genes or Pharmacodynamic Genes?","authors":"Nan Zheng,&nbsp;Mengxi Niu,&nbsp;Yannan Zang,&nbsp;Hongyan Zhuang,&nbsp;Fei Jia,&nbsp;Shuang Bao,&nbsp;Shanshan Liu","doi":"10.2174/1389200224666230907093349","DOIUrl":"10.2174/1389200224666230907093349","url":null,"abstract":"<p><p>Drug therapy is the primary modality for depression; however, its outcome is often unpredictable, ranging from beneficial effects to serious adverse effects. Genetic variations in drug metabolizing enzymes and pharmacodynamic molecules are responsible for a considerable proportion of interindividual differences in the effectiveness and toxicity of antidepressants. For the improvement in the use of antidepressants, the focus is mainly on personalized treatment emphasizing interindividual differences in genes. This study provides a comprehensive review of the literature on the clinical applications of pharmacogenomics for antidepressant therapy. The polymorphisms of metabolizing enzymes (<i>CYP2D6, CYP2C19</i>, and others) governing the pharmacokinetic behavior of drugs are potential predictors of side effects or treatment failure with medications and there are good pharmacogenetic clinical recommendations for a wide selection of psychopharmacological agents based on functional diplotypes of <i>CYP2C19</i> and <i>CYP2D6</i>. The relationship between pharmacodynamic genes, including <i>FKBP5, SLC6A4, BDNF, ABCB1, HTR1A</i>, and <i>HTR2A</i>, and clinical outcomes varies in different races. Receptors that are currently used as drug targets for antidepressant drugs are evolutionarily conserved to a higher extent than genes encoding drug metabolism, and the actionability of pharmacodynamic-related genotyping is currently still questionable. The limited availability of largescale, long-term clinical studies on different races and medications currently impedes the implementation of pharmacogenomics in antidepressant treatment. The use of pharmacokinetic and pharmacodynamic modeling, and therapeutic drug monitoring combined with genetic, somatic, dietary, and environmental factors represents a promising avenue for improving the precision and effectiveness of antidepressant therapy.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10257113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In-vitro</i> and <i>In-vivo</i> Identification, Absorbtion and Metabolism Network Analysis of <i>Filifolium sibiricum</i> Flavonoids Dropping Pill by UHPLC-Q-TOF-MS.","authors":"Rui-Ting Ma,&nbsp;Ji-Xin Han,&nbsp;Jun-Chan Qiao,&nbsp;Li-Jun Tong,&nbsp;Li-Xia Chen","doi":"10.2174/1389200224666230202144113","DOIUrl":"https://doi.org/10.2174/1389200224666230202144113","url":null,"abstract":"<p><strong>Background: </strong>Filifolium sibiricum flavonoids dropping pill (FSFp), a unique Chinese Filifolii sibirici herba extract preparation, has the potential as an alternative therapy against S. aureus infection (SA) and antiinfection. However, its chemical composition and in vivo metabolism characteristics remain unknown, which limits its clinical application.</p><p><strong>Methods: </strong>Here, we aimed to understand the in vitro and in vivo material basis of FSFp. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was used to identify chemicals in FSFp as well as its phase I and phase II reaction metabolites in plasma, urine and feces.</p><p><strong>Results: </strong>A total of 38 chemicals were characterized in FSFp, including 22 flavonoids, 10 organic acids, 3 chromones, 1 aromatic ketone, 1 coumarin, and 1 ligan. After analysis of the drugged bio-samples, a total of 21 compounds were found in urine, and 16 of them were found in feces, but only one was found in plasma. In addition, 56 FSFp-related metabolites were characterized, of which 56 were in urine, 4 in feces, and 8 in plasma.</p><p><strong>Conclusion: </strong>This is the first comprehensive research of FSFp on chemical constituents and metabolic profiles. It was expected that this study would offer reliable support for further investigation of FSFp.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9422920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}