Drug metabolism and personalized therapy最新文献

{"title":"Pharmacogenetic aspects of efficacy and safety of methotrexate treatment in pediatric acute lymphoblastic leukemia.","authors":"Oksana Dmitryevna Gurieva, Marina Ivanovna Savelyeva, Timur Tejmurazovich Valiev, Zhannet Alimovna Sozaeva, Svetlana Nikolaevna Kondratenko, Mikhail Vitalyevich Ilyin","doi":"10.1515/dmpt-2023-0079","DOIUrl":"10.1515/dmpt-2023-0079","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the role of ABCB1 (C3435T rs1045642, rs1128503, rs2032582, rs4148738), SLCO1B1 T521C rs4149056 genetic polymorphisms in the development of major types of methotrexate (MTX) toxicities and the occurrence of a terminal event (death, relapse) in pediatric АLL.</p><p><strong>Methods: </strong>The study included 124 patients diagnosed with pediatric ALL. All patients treated according to the protocols of the German BFM group (2002/2009) with high-dose (1,000, 2,000 and 5,000 mg/m²) methotrexate. MTX-related toxicities, including hematologic, hepatic and renal, were evaluated according to the common terminology criteria for adverse events version 5.0 (CTCAE v.5.0). Real-time PCR method was used to investigate polymorphisms of ABCB1 and SLCO1B1 genes. The study material was peripheral blood.</p><p><strong>Results: </strong>A competitive analysis demonstrated significant relationships between MTX ADRs. The results of the study support the existence of relationships between some ADRs and MTX kinetics. An associative analysis showed association with the development of AEs to methotrexate indicating their clinical significance from different genetic polymorphisms protein-transporters. The available results confirm the associations of the studied genes with the increased risk of high doses MTX toxic ADRs and terminal events.</p><p><strong>Conclusions: </strong>Complementing the existing criteria for pediatric ALL risk groups with pharmacogenetic indicators will allow further individualization of therapy.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"349-357"},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ancestromics.","authors":"Ingrid Fricke-Galindo, Adrián LLerena","doi":"10.1515/dmpt-2023-0089","DOIUrl":"10.1515/dmpt-2023-0089","url":null,"abstract":"","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"38 4","pages":"293"},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ancestromics.","authors":"Ingrid Fricke-Galindo, Adrián LLerena","doi":"10.1515/dmdi-2023-0089","DOIUrl":"https://doi.org/10.1515/dmdi-2023-0089","url":null,"abstract":"","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of CYP2D6 allelic variants on therapy with tamsulosin in patients with benign prostatic hyperplasia.","authors":"Skokhrukh P Abdullaev, Maksim N Shatokhin, Svetlana N Tuchkova, Sherzod P Abdullaev, Oleg V Teodorovich, Oleg B Loran, Dmitry A Sychev","doi":"10.1515/dmpt-2023-0050","DOIUrl":"10.1515/dmpt-2023-0050","url":null,"abstract":"<p><strong>Objectives: </strong>Tamsulosin is a first-line drug for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Despite its high ratings for efficacy and safety, these parameters may vary due to genetic polymorphisms of CYP2D6 enzyme, which is involved in the metabolism of the drug. This variability may have great impact on the therapy of LUTS associated with BPH and may require an individualized approach to drug selection. The aim of the study was to assess the impact of genetic polymorphisms in CYP2D6 on the efficacy and safety of tamsulosin therapy in patients with LUTS associated with BPH.</p><p><strong>Methods: </strong>The study included 106 patients with LUTS/BPH (N40 according to ICD-10). All patients received monotherapy with tamsulosin 0.4 mg/day for at least 8 weeks. Depending on the severity of symptoms, all patients were divided into 2 groups based on the IPSS score: the first group of patients had moderate symptoms (n=57), and the second group of patients had severe symptoms (n=49). The results of treatment were assessed using the IPSS questionnaire with determination of quality of life (QoL), transrectal ultrasound of the prostate with determination of prostate volume and postvoid residual urine volume, and uroflowmetry. The carriage of allelic variants of CYP2D6 (*3, *4, *9, *10, and *41) were determined by polymerase chain reaction in all patients.</p><p><strong>Results: </strong>In patients with moderate symptoms who was classified as «intermediate» metabolizers by CYP2D6, a statistically significant greater reduction in symptoms according to the overall IPSS scale at 8 weeks (p=0.046) and the obstructive symptom subscale starting from 4 weeks of treatment (p<0.05) was shown. Allelic variants of the CYP2D6 gene did not affect the frequency of adverse reactions to tamsulosin.</p><p><strong>Conclusions: </strong>The results of the study show that in patients with moderate LUTS associated with BPH who are «intermediate» metabolizers by CYP2D6, there is a better therapeutic effect of tamsulosin.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"323-330"},"PeriodicalIF":0.0,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10127131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontmatter","authors":"","doi":"10.1515/dmpt-2023-frontmatter3","DOIUrl":"https://doi.org/10.1515/dmpt-2023-frontmatter3","url":null,"abstract":"","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"77 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135299703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relevance of personalized medicine for improving traditional medicine.","authors":"Ingrid Fricke-Galindo,&nbsp;Adrián LLerena","doi":"10.1515/dmdi-2023-0068","DOIUrl":"https://doi.org/10.1515/dmdi-2023-0068","url":null,"abstract":"","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10407770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PDE5 inhibitors: breaking new grounds in the treatment of COVID-19.","authors":"Ryan Varghese, Gargi Digholkar, Jainam Karsiya, Sahil Salvi, Jeenam Shah, Dileep Kumar, Rohit Sharma","doi":"10.1515/dmpt-2023-0011","DOIUrl":"10.1515/dmpt-2023-0011","url":null,"abstract":"<p><strong>Introduction: </strong>Despite the ever-increasing occurrences of the coronavirus disease (COVID-19) cases around the world, very few medications have been validated in the clinical trials to combat COVID-19. Although several vaccines have been developed in the past quarter, the time elapsed between deployment and administration remains a major impediment.</p><p><strong>Content: </strong>Repurposing of pre-approved drugs, such as phosphodiesterase 5 (PDE5) inhibitors, could be a game-changer while lessening the burden on the current healthcare system. Repurposing and developing phosphodiesterase 5 (PDE5) inhibitors could extrapolate their utility to combat the SARS-CoV-2 infection, and potentially aid in the management of the symptoms associated with its newer variants such as BF.7, BQ.1, BQ.1.1, XBB.1.5, and XBB.1.16.</p><p><strong>Summary: </strong>Administration of PDE5 inhibitors via the oral and intravenous route demonstrates other potential off-label benefits, including anti-apoptotic, anti-inflammatory, antioxidant, and immunomodulatory effects, by intercepting several pathways. These effects can not only be of clinical importance in mild-to-moderate, but also moderate-to-severe SARS-CoV-2 infections. This article explores the various mechanisms by which PDE5 inhibitors alleviates the symptoms associated with COVID-19 as well as well as highlights recent studies and findings.</p><p><strong>Outlook: </strong>These benefits of PDE5 inhibitors make it a potential drug in the physicians' armamentarium in alleviating symptoms associated with SARS-CoV-2 infection. However, adequate clinical studies must be instituted to eliminate any untoward adverse events.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"38 4","pages":"295-307"},"PeriodicalIF":0.0,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PDE5 inhibitors: breaking new grounds in the treatment of COVID-19.","authors":"Ryan Varghese,&nbsp;Gargi Digholkar,&nbsp;Jainam Karsiya,&nbsp;Sahil Salvi,&nbsp;Jeenam Shah,&nbsp;Dileep Kumar,&nbsp;Rohit Sharma","doi":"10.1515/dmdi-2023-0011","DOIUrl":"https://doi.org/10.1515/dmdi-2023-0011","url":null,"abstract":"<p><strong>Introduction: </strong>Despite the ever-increasing occurrences of the coronavirus disease (COVID-19) cases around the world, very few medications have been validated in the clinical trials to combat COVID-19. Although several vaccines have been developed in the past quarter, the time elapsed between deployment and administration remains a major impediment.</p><p><strong>Content: </strong>Repurposing of pre-approved drugs, such as phosphodiesterase 5 (PDE5) inhibitors, could be a game-changer while lessening the burden on the current healthcare system. Repurposing and developing phosphodiesterase 5 (PDE5) inhibitors could extrapolate their utility to combat the SARS-CoV-2 infection, and potentially aid in the management of the symptoms associated with its newer variants such as BF.7, BQ.1, BQ.1.1, XBB.1.5, and XBB.1.16.</p><p><strong>Summary: </strong>Administration of PDE5 inhibitors via the oral and intravenous route demonstrates other potential off-label benefits, including anti-apoptotic, anti-inflammatory, antioxidant, and immunomodulatory effects, by intercepting several pathways. These effects can not only be of clinical importance in mild-to-moderate, but also moderate-to-severe SARS-CoV-2 infections. This article explores the various mechanisms by which PDE5 inhibitors alleviates the symptoms associated with COVID-19 as well as well as highlights recent studies and findings.</p><p><strong>Outlook: </strong>These benefits of PDE5 inhibitors make it a potential drug in the physicians' armamentarium in alleviating symptoms associated with SARS-CoV-2 infection. However, adequate clinical studies must be instituted to eliminate any untoward adverse events.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10052200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relevance of personalized medicine for improving traditional medicine.","authors":"Ingrid Fricke-Galindo,&nbsp;Adrián LLerena","doi":"10.1515/dmpt-2023-0068","DOIUrl":"10.1515/dmpt-2023-0068","url":null,"abstract":"","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"38 3","pages":"209-210"},"PeriodicalIF":0.0,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10286683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemical profiling and biological activities of <i>Diplazium esculentum</i> (Retz.) Sw.: an edible vegetable fern.","authors":"Kirti Raina, Alisha Chaudhary, Purnima Sharma, Rohit Sharma, Kanchan Bhardwaj, Pardeep Kumar, Atul Kabra, Sunil Thakur, Ashun Chaudhary, Mamta Prajapati, Pradeep Kumar Prajapati, Rajeev K Singla, Rohit Sharma","doi":"10.1515/dmpt-2023-0035","DOIUrl":"10.1515/dmpt-2023-0035","url":null,"abstract":"<p><strong>Objectives: </strong><i>Diplazium esculentum</i> (Retz.) Sw. is an edible vegetable fern of the Himalayan region with high nutritional and therapeutic value owing to its richness in various secondary metabolites and both macro and micronutrients.</p><p><strong>Content: </strong>This updated review discusses the general traditional use, ethnopharmacology, phytochemistry, nutritional value, pharmacology, and toxicity concerns of <i>D. esculentum.</i></p><p><strong>Summary: </strong>The plant parts, viz. rhizomes, shoots, fronds and leaves, have immense ethnomedicinal importance, being traditionally used to cure several health disorders. Among other pharmacological effects, this botanical reveals excellent anti-inflammatory, analgesic, antifungal, antibacterial, antioxidant, anti-leishmanial, antioxidant, anaphylactic, antipyretic, anthelmintic and hepatoprotective activities, directly attributed to the presence of many secondary metabolites. From a pharmacological point of view, the excellent antioxidant potential of <i>D. esculentum</i> suggests its promising use for nutraceutical or functional food formulation purposes.</p><p><strong>Outlook: </strong>Considering the evidences on popular ethnomedicinal uses of <i>D. esculentum</i> as an edible vegetable, its immense bio-potential, and multiple pharmacological roles, there is a huge need to evaluate its therapeutic applications in light of standard clinical trials.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"309-322"},"PeriodicalIF":0.0,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9924432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}