Current drug metabolism最新文献

{"title":"Role of Cytochrome P450 3A4 in Cancer Drug Resistance: Challenges and Opportunities.","authors":"Swaroop Kumar Pandey, Sona Verma, Shobha Upreti, Anuja Mishra, Neha Yadav, Hemlata Dwivedi-Agnihotri","doi":"10.2174/0113892002312369240703102215","DOIUrl":"10.2174/0113892002312369240703102215","url":null,"abstract":"<p><p>One of the biggest obstacles to the treatment of diseases, particularly serious conditions like cancer, is therapeutic resistance. The process of drug resistance is influenced by a number of important variables, including MDR genes, drug efflux, low-quality medications, inadequate dosage, etc. Drug resistance must be addressed, and new combinations based on the pharmacokinetics/pharmacodynamics (PK-PD) characteristics of the partner pharmaceuticals must be developed in order to extend the half-lives of already available medications. The primary mechanism of drug elimination is hepatic biotransformation of medicines by cytochrome P450 (CYP) enzymes; of these CYPs, CYP3A4 makes up 30-40% of all known cytochromes that metabolize medications. Induction or inhibition of CYP3A4-mediated metabolism affects the pharmacokinetics of most anticancer drugs, but these details are not fully understood and highlighted because of the complexity of tumor microenvironments and various influencing patient related factors. The involvement of CYPs, particularly CYP3A4 and other drug-metabolizing enzymes, in cancer medication resistance will be covered in the current review.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"235-247"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562879","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":"Study on Cytochrome P450 Metabolic Profile of Paclitaxel on Rats using QTOF-MS.","authors":"Zhaoyang Meng, Junjun Chen, Lingyan Xu, Xiao Xiao, Ling Zong, Yonglong Han, Bo Jiang","doi":"10.2174/0113892002308509240711100502","DOIUrl":"10.2174/0113892002308509240711100502","url":null,"abstract":"<p><strong>Background: </strong>Paclitaxel (PTX) is a key drug used for chemotherapy for various cancers. The hydroxylation metabolites of paclitaxel are different between humans and rats. Currently, there is little information available on the metabolic profiles of CYP450 enzymes in rats.</p><p><strong>Objective: </strong>This study evaluated the dynamic metabolic profiles of PTX and its metabolites in rats and <i>in vitro</i>.</p><p><strong>Methods: </strong>Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and LC-MS/MS were applied to qualitative and quantitative analysis of PTX and its metabolites in rats, liver microsomes and recombinant enzyme CYP3A1/3A2. Ten specific inhibitors [NF (CYP1A1), FFL (CYP1A2), MOP (CYP2A6), OND (CYP2B6), QCT (CYP2C8), SFP (CYP2C9), NKT (CYP2C19), QND (CYP2D6), MPZ (CYP2E1) and KTZ (CYP3A4)] were used to identify the metabolic pathway <i>in vitro</i>.</p><p><strong>Results: </strong>Four main hydroxylated metabolites of PTX were identified. Among them, 3'-p-OH PTX and 2-OH PTX were monohydroxylated metabolites identified in rats and liver microsome samples, and 6α-2-di-OH PTX and 6α-5\"-di-OH PTX were dihydroxylated metabolites identified in rats. CYP3A recombinant enzyme studies showed that the CYP3A1/3A2 in rat liver microsomes was mainly responsible for metabolizing PTX into 3'-p- OH-PTX and 2-OH-PTX. However, 6α-OH PTX was not detected in rat plasma and liver microsome samples.</p><p><strong>Conclusion: </strong>The results indicated that the CYP3A1/3A2 enzyme, metabolizing PTX into 3'-p-OH-PTX and 2- OH-PTX, is responsible for the metabolic of PTX in rats. The CYP2C8 metabolite 6α-OH PTX in humans was not detected in rat plasma in this study, which might account for the interspecies metabolic differences between rats and humans. This study will provide evidence for drug-drug interaction research in rats.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"330-339"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747621","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":"Quality by Design Approach for the Development of Cariprazine Hydrochloride Loaded Lipid-Based Formulation for Brain Delivery <i>via</i> Intranasal Route.","authors":"Pallavi Chiprikar, Vinayak Mastiholimath, Prakash Biradar, Nisha Shirkoli","doi":"10.2174/0113892002327148240924071717","DOIUrl":"10.2174/0113892002327148240924071717","url":null,"abstract":"<p><strong>Background: </strong>Cariprazine (CPZ) is a third-generation antipsychotic medication that has been approved for treating schizophrenia. This study aimed to develop a cariprazine-loaded nanostructured lipid carrier (CPZ-NLCs) to prevent first-pass metabolism and improve bioavailability and site-specific delivery from nose to the brain.</p><p><strong>Methods: </strong>The CPZ-NLCs were prepared using melt emulsification. The formulation was optimized using the Box-Behnken design (BBD); where the influence of independent variables on critical quality attributes, such as particle size and entrapment efficiency was studied.</p><p><strong>Results: </strong>The optimized batch (F6) had a particle size of 173.3 ± 0.6 nm and an entrapment efficiency of 96.1 ± 0.57%, respectively. The in vitro release showed >96% release of CPZ from NLC within 30 min. The optimized formulation's ex vivo studies revealed significantly increased CPZ permeability (>75%) in sheep nasal mucosa compared to the CPZ suspension (~26%). The ciliotoxicity study of the nasal mucosa revealed that the CPZ-NLC formulation did not affect the nasal epithelium. The intranasal administration of the formulation achieved 76.14±6.23 μg/ml concentration in the brain which was significantly higher than the oral CPZ suspension administration (30.46±7.24 μg/ml). The developed formulation was stable for 3 months.</p><p><strong>Conclusion: </strong>The study concluded that the developed CPZ-NLC could significantly improve the bioavailability with quick delivery to the brain.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"523-541"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371198","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":"Avapritinib Carries the Risk of Drug Interaction <i>via</i> Inhibition of UDP-Glucuronyltransferase (UGT) 1A1.","authors":"Xin Lv, Zhen Wang, Zhe Wang, Hang Yin, Yangliu Xia, Lili Jiang, Yong Liu","doi":"10.2174/0113892002288312240521092054","DOIUrl":"10.2174/0113892002288312240521092054","url":null,"abstract":"<p><strong>Background: </strong>Avapritinib is the only drug for adult patients with PDGFRA exon 18 mutated unresectable or metastatic gastrointestinal stromal tumor (GIST). Although avapritinib has been approved by the FDA for four years, little is known about the risk of drug-drug interactions (DDIs) via UDP-glucuronyltransferases (UGTs) inhibition.</p><p><strong>Objective: </strong>The aim of the present study was to systematically evaluate the inhibitory effects of avapritinib against UGTs and to quantitatively estimate its potential DDIs risk <i>in vivo</i>.</p><p><strong>Methods: </strong>Recombinant human UGTs were employed to catalyze the glucuronidation of substrates in a range of concentrations of avapritinib. The kinetics analysis was performed to evaluate the inhibition types of avapritinib against UGTs. The quantitative prediction of DDIs was done using <i>in vitro-in vivo</i> extrapolation (IVIVE).</p><p><strong>Results: </strong>Avapritinib had a potent competitive inhibitory effect on UGT1A1. Quantitative prediction results showed that avapritinib administered at clinical doses might result in a 14.85% increase in area under the curve (AUC) of drugs primarily cleared by UGT1A1. Moreover, the Rgut value was calculated to be 18.44.</p><p><strong>Conclusion: </strong>Avapritinib has the potential to cause intestinal DDIs <i>via</i> the inhibition of UGT1A1. Additional attention should be paid when avapritinib is coadministered with UGT1A1 substrates.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"197-204"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157928","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":"Disposition Kinetics of Cathinone and its Metabolites after Oral Administration in Rats.","authors":"Fahad Y Sabei, Ibrahim Khardali, Mohamed A Al-Kasim, Emad Sayed Shaheen, Magbool Oraiby, Ahmad Alamir, Banji David, Saeed Alshahrani, Abdulmajeed M Jali, Mohammed Attafi, Mohammed Y Albeishy, Ibraheem Attafi","doi":"10.2174/0113892002300638240513065512","DOIUrl":"10.2174/0113892002300638240513065512","url":null,"abstract":"<p><strong>Background: </strong>Cathinone is a natural stimulant found in the Catha edulis plant. Its derivatives make up the largest group of new psychoactive substances. In order to better understand its effects, it is imperative to investigate its distribution, pharmacokinetics, and metabolic profile. However, the existing literature on cathinone remains limited.</p><p><strong>Objective: </strong>This study aimed to investigate the disposition kinetics and metabolic profile of cathinone and its metabolite cathine through a single oral dose of cathinone administration in rats.</p><p><strong>Methods: </strong>Cathinone and cathine concentrations were identified and quantified using ion trap liquid chromatography- mass spectrometry (LC-IT/MS). The metabolic profile in the serum, brain, lung, liver, kidney, and heart was analyzed at specific time points (0, 0.5, 2.5, 6, 12, 24, 48, and 72 hours) using the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) method.</p><p><strong>Results: </strong>The highest concentration of cathinone was found in the kidney (1438.6 μg/L, which gradually decreased to 1.97 within 48 h and disappeared after 72 h. Cathinone levels in the lungs, liver, and heart were 859, 798.9, and 385.8 μg/L, respectively, within half an hour. However, within 2.5 hours, these levels decreased to 608.1, 429.3, and 309.1 μg/L and became undetectable after 24 h. In the rat brain, cathinone levels dropped quickly and were undetectable within six hours, decreasing from 712.7 μg/L after 30 min. In the brain and serum, cathine reached its highest levels at 2.5 hours, while in other organs, it peaked at 0.5 hours, indicating slower conversion of cathinone to cathine in the brain and serum.</p><p><strong>Conclusion: </strong>This study revealed a dynamic interplay between cathinone disposition kinetics and its impact on organ-specific metabolic profiles in rats. These results have significant implications for drug development, pharmacovigilance, and clinical practices involving cathinone. Investigating the correlation between the changes in biomarkers found in the brain and the levels of cathinone and cathine is essential for informed decision- making in medical practices and further research into the pharmacological properties of cathinone.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"220-226"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944368","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":"Hydrogen Peroxide Induces Ethanol-inducible CYP2E1 <i>via</i> the NF-kB-classical Pathway: CYP2E1 mRNA Levels are not High in Alcoholic Hepatitis.","authors":"Akiyoshi Tamura, Ferbian Milas Siswanto, Takumi Yoshimura, Ami Oguro, Susumu Imaoka","doi":"10.2174/0113892002305174240805064406","DOIUrl":"10.2174/0113892002305174240805064406","url":null,"abstract":"<p><strong>Aims: </strong>The aim of the present study is to elucidate the mechanism of CYP2E1 induction as a causative factor of Alcoholic Hepatitis (AH) and its relationship with inflammation.</p><p><strong>Background: </strong>Chronic alcohol consumption induces CYP2E1, which is involved in the development of Alcoholic Hepatitis (AH). However, the mechanisms underlying the induction of CYP2E1 by alcohol remain unclear. Therefore, we herein investigated the induction of drug-metabolizing enzymes, particularly CYP2E1, by hydrogen peroxide (H₂O₂), the concentration of which is elevated under inflammatory conditions.</p><p><strong>Objective: </strong>The mechanisms underlying the induction of CYP2E1 by H₂O₂ were examined with a focus on Keap1, a target factor of H₂O₂.</p><p><strong>Methods: </strong>We assessed changes in the expression of drug-metabolizing enzymes in the human hepatoma cell line, Hep3B, following treatment with H₂O₂, and evaluated changes in the expression of the NF-kB-related factor RelA(p65) after the knockdown of Keap1, a regulator of Nrf2 expression by reactive oxygen species. We also performed a promoter analysis using the upstream region of the CYP2E1 gene. We herein used the GSE89632 series for non-alcoholic hepatitis (NASH) and the GSE28619 series for AH.</p><p><strong>Results: </strong>The induction of CYP2E1 by H₂O₂ was significantly stronger than that of other drugmetabolizing enzymes. On the other hand, the knockdown of Keap1, a target of H₂O₂, markedly increased RelA(p65), an NFkB factor. Furthermore, the overexpression of RelA(p65) strongly induced the expression of CYP2E1. Four candidate p65-binding sequences were identified upstream of the CYP2E1 gene, and promoter activity assays showed that the third sequence was responsive to the overexpression of RelA(p65). We used the GSE89632 series for NASH and the GSE28619 series for AH in the present study. The expression of CYP2E1 mRNA in the liver was significantly lower in AH patients than in HC patients, but was similar in HC patients and NASH patients.</p><p><strong>Conclusion: </strong>We herein demonstrated that the expression of CYP2E1 was induced by H₂O₂. The overexpression of RelA(p65) also induced CYP2E1 mRNA expression, whereas H₂O₂ did not after the knockdown of RelA. These results suggest that H₂O₂ acts on Keap1 to upregulate RelA (p65) in the NFkB system. One of the mechanisms underlying the induction of CYP2E1 was dependent on the H₂O₂-Keap1-RelA axis. The results of the database analysis revealed that the expression of CYP2E1 in the liver was significantly lower in AH patients than in NASH patients, suggesting that CYP2E1 is not the main cause of AH; however, CYP2E1 may exacerbate the pathogenesis of AH.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"307-316"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916270","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":"Recent Advances in Hepatic Metabolic Regulation by the Nuclear Factor Rev-erbɑ.","authors":"Qi Zhang, Yutong Chen, Jingqi Li, Haishan Xia, Yongbin Tong, Yuyu Liu","doi":"10.2174/0113892002290055240212074758","DOIUrl":"10.2174/0113892002290055240212074758","url":null,"abstract":"<p><p>Rev-erbɑ (NR1D1) is a nuclear receptor superfamily member that plays a vital role in mammalian molecular clocks and metabolism. Rev-erbɑ can regulate the metabolism of drugs and the body's glucose metabolism, lipid metabolism, and adipogenesis. It is even one of the important regulatory factors regulating the occurrence of metabolic diseases (e.g., diabetes, fatty liver). Metabolic enzymes mediate most drug metabolic reactions in the body. Rev-erbɑ has been recognized to regulate drug metabolic enzymes (such as Cyp2b10 and Ugt1a9). Therefore, this paper mainly reviewed that Rev-erbɑ regulates I and II metabolic enzymes in the liver to affect drug pharmacokinetics. The expression of these drug metabolic enzymes (up-regulated or down-regulated) is related to drug exposure and effects/ toxicity. In addition, our discussion extends to Rev-erbɑ regulating some transporters (such as P-gp, Mrp2, and Bcrp), as they also play an essential role in drug metabolism. Finally, we briefly describe the role and mechanism of nuclear receptor Rev-erbɑ in lipid and glucose homeostasis, obesity, and metabolic disorders syndrome. In conclusion, this paper aims to understand better the role and mechanism of Rev-erbɑ in regulating drug metabolism, lipid, glucose homeostasis, obesity, and metabolic disorders syndrome, which explores how to target Rev-erbɑ to guide the design and development of new drugs and provide scientific reference for the molecular mechanism of new drug development, rational drug use, and drug interaction.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"2-12"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971187","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":"Unraveling the Role of COMT Polymorphism in Dopamine-Mediated Vasopressor Effects: An Observational Cross-Sectional Study.","authors":"Kannan Sridharan, Anfal Jassim, Ali Mohammed Qader, Sheikh Abdul Azeez Pasha","doi":"10.2174/0113892002293952240315064943","DOIUrl":"10.2174/0113892002293952240315064943","url":null,"abstract":"<p><strong>Aims: </strong>To evaluate the association between rs4680 polymorphism in the COMT gene and the vasoconstrictive effects of commonly used vasopressors.</p><p><strong>Background: </strong>Dopamine is a medication that is given intravenously to critically ill patients to help increase blood pressure. Catechol O-Methyl Transferase (COMT) breaks down dopamine and other catecholamines. There is a genetic variation in the COMT gene called rs4680 that can affect how well the enzyme works. Studies have shown that people with this genetic variation may have different blood pressure levels. However, no one has looked at how this genetic variation affects the way dopamine works to increase blood pressure.</p><p><strong>Objectives: </strong>To investigate the impact of the rs4680 polymorphism in the COMT gene on the pharmacodynamic response to dopamine.</p><p><strong>Methods: </strong>Critically ill patients administered dopamine were included following the consent of their legally acceptable representatives. Details on their demographic characteristics, diagnosis, drug-related details, changes in the heart rate, blood pressure, and urinary output were obtained. The presence of rs4680 polymorphism in the COMT gene was evaluated using a validated method.</p><p><strong>Results: </strong>One hundred and seventeen patients were recruited, and we observed a prevalence of rs4680 polymorphism in 57.3% of our critically ill patients. Those with mutant genotypes were observed with an increase in the median rate of change in mean arterial pressure (mm Hg/hour) [wild: 8.9 (-22.6 to 49.1); heterozygous mutant: 5.9 (-34.1 to 61.6); and homozygous mutant: 19.5 (-2.5 to 129.2)] and lowered urine output (ml/day) [wild: 1080 (21.4 to 5900); heterozygous mutant: 380 (23.7 to 15800); and homozygous mutant: 316.7 (5.8 to 2308.3)].</p><p><strong>Conclusion: </strong>V158M (rs4680) polymorphism is widely prevalent in the population and was significantly associated with altered effects as observed clinically. This finding suggests valuable insights into the molecular basis of COMT function and its potential impact on neurotransmitter metabolism and related disorders. Large-scale studies delineating the effect of these polymorphisms on various vasopressors are the need of the hour.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"152-156"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174064","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":"Association of <i>UGT1A</i> Gene Polymorphisms with BKV Infection in Renal Transplantation Recipients.","authors":"Jingwen Yuan, Shuang Fei, Zeping Gui, Zijie Wang, Hao Chen, Li Sun, Jun Tao, Zhijian Han, Xiaobing Ju, Ruoyun Tan, Min Gu, Zhengkai Huang","doi":"10.2174/0113892002282727240307072255","DOIUrl":"10.2174/0113892002282727240307072255","url":null,"abstract":"<p><strong>Background: </strong>BK virus (BKV) infection is an opportunistic infectious complication and constitutes a risk factor for premature graft failure in kidney transplantation. Our research aimed to identify associations and assess the impact of single-nucleotide polymorphisms (SNPs) on metabolism-related genes in patients who have undergone kidney transplantation with BKV infection.</p><p><strong>Material/methods: </strong>The DNA samples of 200 eligible kidney transplant recipients from our center, meeting the inclusion criteria, have been collected and extracted. Next-generation sequencing was used to genotype SNPs on metabolism-associated genes (CYP3A4/5/7, UGT1A4/7/8/9, UGT2B7). A general linear model (GLM) was used to identify and eliminate confounding factors that may influence the outcome events. Multiple inheritance models and haplotype analyses were utilized to identify variation loci associated with infection caused by BKV and ascertain haplotypes, respectively.</p><p><strong>Results: </strong>A total of 141 SNPs located on metabolism-related genes were identified. After Hardy-Weinberg equilibrium (HWE) and minor allele frequency (MAF) analysis, 21 tagger SNPs were selected for further association analysis. Based on GLM results, no confounding factor was significant in predicting the incidence of BK polyomavirus-associated infection. Then, multiple inheritance model analyses revealed that the risk of BKV infection was significantly associated with rs3732218 and rs4556969. Finally, we detect significant associations between haplotype T-A-C of block 2 (rs4556969, rs3732218, rs12468274) and infection caused by BKV (P = 0.0004).</p><p><strong>Conclusion: </strong>We found that genetic variants in the UGT1A gene confer BKV infection susceptibility after kidney transplantation.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"188-196"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174062","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":"Safety Aspects of Herb Interactions: Current Understanding and Future Prospects.","authors":"Subhajit Hazra, Preet Amol Singh","doi":"10.2174/0113892002289753240305062601","DOIUrl":"10.2174/0113892002289753240305062601","url":null,"abstract":"<p><strong>Background: </strong>The use of herbal medicines is on the rise throughout the world due to their perceived safety profile. However, incidences of herb-drug, herb-herb and herb-food interactions considering safety aspects have opened new arenas for discussion.</p><p><strong>Objective: </strong>The current study aims to provide comprehensive insights into the various types of herb interactions, the mechanisms involved, their assessment, and historical developments, keeping herbal safety at the central point of discussion.</p><p><strong>Methods: </strong>The authors undertook a focused/targeted literature review and collected data from various databases, including Science Direct, Wiley Online Library, Springer, PubMed, and Google Scholar. Conventional literature on herbal remedies, such as those by the WHO and other international or national organizations.</p><p><strong>Results: </strong>The article considered reviewing the regulations, interaction mechanisms, and detection of herb-herb, herb-drug and herb-food interactions in commonly used yet vital plants, including <i>Glycyrrhiza glabra, Mentha piperita, Aloe barbadensis, Zingiber officinale, Gingko biloba, Withania somnifera, etc</i>. The study found that healthcare professionals worry about patients not informing them about their herbal prescriptions (primarily used with conventional treatment), which can cause herb-drug/herb-food/herb-herb interactions. These interactions were caused by altered pharmacodynamic and pharmacokinetic processes, which might be explained using <i>in-vivo, in-vitro, in-silico</i>, pharmacogenomics, and pharmacogenetics. Nutrivigilance may be the greatest method to monitor herb-food interactions, but its adoption is limited worldwide.</p><p><strong>Conclusion: </strong>This article can serve as a lead for clinicians, guiding them regarding herb-drug, herb-food, and herb-herb interactions induced by commonly consumed plant species. Patients may also be counseled to avoid conventional drugs, botanicals, and foods with a restricted therapeutic window.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"28-53"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119027","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}