Drug metabolism and personalized therapy最新文献

{"title":"CYP2D6 inhibition by diphenhydramine leading to fatal hydrocodone overdose.","authors":"Aaron G Whitt, Saeed A Jortani","doi":"10.1515/dmpt-2023-0081","DOIUrl":"10.1515/dmpt-2023-0081","url":null,"abstract":"<p><strong>Objectives: </strong>Fatal drug overdoses often involve multiple co-intoxicants, including opioids. Hydrocodone, the most prescribed opioid for pain management, is metabolized to the active metabolite hydromorphone by hepatic CYP2D6. Inhibition of CYP2D6 by other compounds can disrupt the analgesic properties of hydrocodone and extend its half-life. Diphenhydramine is an over-the-counter cold medication and is known to inhibit CYP2D6 activity.</p><p><strong>Case presentation: </strong>A woman in her late 50s was prescribed hydrocodone/acetaminophen (Norco^® 10/325). Days before her death, she began taking diphenhydramine for cold symptoms. A post-mortem toxicology report detected the following compounds by High Performance Liquid Chromatography/Time of Flight-Mass Spectrometry (LC/TOF-MS) analysis: acetaminophen (14 μg/mL), hydrocodone (410 ng/mL), dihydrocodeine (24 ng/mL), and diphenhydramine (150 ng/mL). Hydromorphone was not detected (<2 ng/mL). All compounds were detected in therapeutic concentrations, except for hydrocodone, which was present at lethal concentrations.</p><p><strong>Conclusions: </strong>This case highlights a fatal drug-drug interaction between hydrocodone and diphenhydramine. The estimated total body burden of hydrocodone was 6- to 12-fold higher than acetaminophen, which is unexpected, as these two drugs were administered as a single formulation and have similar half-lives. Furthermore, hydromorphone was undetectable. Taken together, these findings are highly suggestive of a fatal opioid overdose precipitated by diphenhydramine.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"99-102"},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916204","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":"Impact of <i>ABCB1</i> genetic polymorphism on carbamazepine dose requirement among Southern Indian persons with epilepsy.","authors":"Elango Dhivya, Ramasamy Kesavan, Nair P Pradeep","doi":"10.1515/dmpt-2023-0054","DOIUrl":"10.1515/dmpt-2023-0054","url":null,"abstract":"<p><strong>Objectives: </strong>Carbamazepine (CBZ) is one of the oldest, yet first line drugs for treating epilepsy. However, there is a large inter-individual difference in requirement of maintenance dose and one third of persons treated with antiepileptic drugs (AEDs) exhibit drug resistance to therapy. One of the proposed mechanisms for the drug resistance was increased expression of efflux transporter P-glycoprotein. The pharmacogenetic studies of drug transporters (<i>ABCB1</i>) done in combination therapies of AEDs were inconclusive. Hence, we have attempted to study the impact of <i>ABCB1 3435C>T</i> genetic polymorphism and CBZ monotherapy in persons with epilepsy (PWE) from South India, which is a genetically distinct population<b>.</b> With this background, this study was aimed to determine the dose of CBZ in <i>ABCB1 3435C>T</i> genotypes and to determine the distribution of <i>ABCB1 3435C>T</i> genotypes (which codes P-glycoprotein) between responders and non-responders to CBZ therapy.</p><p><strong>Methods: </strong>A cross sectional study was conducted in 200 persons with epilepsy, who were categorised as responders and non-responders according to ILAE (international league against epilepsy) criteria. Eligible participants were enrolled from the epilepsy clinic of the neurology department and five ml of blood was collected. DNA extraction and genotyping were done by phenol-chloroform method and real time polymerase chain reaction (RT-PCR), respectively.</p><p><strong>Results: </strong>The mean maintenance dose of carbamazepine was statistically significant among different genotypes (p<0.05) of <i>ABCB1 3435C>T</i> (526 vs. 637 mg/day in CC vs. TT genotype). There was no significant association between <i>ABCB1 3435C>T</i> polymorphism (p=0.827) and CBZ resistance in PWE. Duration of disease and age of onset were found to be significant in predicting the response to CBZ therapy.</p><p><strong>Conclusions: </strong>We report that <i>ABCB1 3435C>T</i> polymorphism is significantly associated with an increase in dose requirement of CBZ in persons with epilepsy from South India.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"27-34"},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174080","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":"Leaders in pharmacogenetics: Urs Albert Meyer","authors":"F. Rodrigues-Soares, I. Fricke-Galindo, Adrián LLerena","doi":"10.1515/dmpt-2024-0016","DOIUrl":"https://doi.org/10.1515/dmpt-2024-0016","url":null,"abstract":"","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"331 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140227772","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":"Nephroprotective effect of cranberry (<i>Vaccinium oxycoccos</i>) in streptozocin-induced diabetic nephropathy in mice.","authors":"Saja Majeed Shareef, Raghad Abdulsalam Khaleel, Taif M Maryoosh","doi":"10.1515/dmpt-2023-0092","DOIUrl":"10.1515/dmpt-2023-0092","url":null,"abstract":"<p><strong>Objectives: </strong>Diabetic nephropathy is a chief reason of mortality particularly in individuals with renal dysfunction. The current research was aimed to assess the nephroprotective portion of <i>Vaccinium oxycoccos</i> toward mice diabetic nephropathy induced by streptozotocin (STZ). <i>V. oxycoccos</i> was purchased and used for hydroalcoholic extraction.</p><p><strong>Methods: </strong>Sixty male mice were subjected to STZ-intraperitoneal injection (45 mg/kg). After diabetes induction, mice were divided into five groups of diabetic control (received only STZ), non-diabetic control (received only citrate buffer), two <i>V. oxycoccos</i> treatment (received <i>V. oxycoccos</i> extract (200 and 400 mg/kg) oral daily by gavage), and metformin treatment (received metformin (500 mg/kg) oral daily by gavage). Glucose and weight of mice were checked weekly.</p><p><strong>Results: </strong>After 28 days, the effect of <i>V. oxycoccos</i> extract on serum and urine parameters were assessed. STZ caused significant decreased in the mice body weight. Mice treated with the <i>V. oxycoccos</i> (400 mg/kg) harbored the lowest weight loss at day 28 (70.2±1.38 g). STZ caused significant increase in the mice FBS. Mice treated with the <i>V. oxycoccos</i> (400 mg/kg) harbored the lowest FBS at day 28 (189.2±1.20 mg/dL). Treatment of mice with <i>V. oxycoccos</i> (400 mg/kg) caused the lowest increase in the levels of cholesterol, HbA_1c and triglycerides compared to the diabetic control mice. Compared to the diabetic control group, mice treated with <i>V. oxycoccos</i> (400 mg/kg) had the highest HDL, insulin, SOD, and GSH (p<0.05). The lowest serum BUN, CR, and UR were found in mice treated with <i>V. oxycoccos</i> (400 mg/kg). Anti-inflammatory effects of <i>V. oxycoccos</i> (400 mg/kg) was shown by the lowest TNF-α, IL-6, and TGF-β1 concentration in mice treated with <i>V. oxycoccos</i> (400 mg/kg).</p><p><strong>Conclusions: </strong>The current study disclosed that treatment with <i>V. oxycoccos</i> resulted in substantial development in the serum and urine parameters and also antioxidant and anti-inflammatory response of STZ-induced diabetic mice.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"35-45"},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101260","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":"Unlocking the potential of oncology biomarkers: advancements in clinical theranostics.","authors":"Ankit Kumar Dubey, Ishnoor Kaur, Reecha Madaan, Shikha Raheja, Rajni Bala, Manoj Garg, Suresh Kumar, Viney Lather, Vineet Mittal, Deepti Pandita, Rohit Gundamaraju, Rajeev K Singla, Rohit Sharma","doi":"10.1515/dmpt-2023-0056","DOIUrl":"10.1515/dmpt-2023-0056","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer biomarkers have revolutionized the field of oncology by providing valuable insights into tumor changes and aiding in screening, diagnosis, prognosis, treatment prediction, and risk assessment. The emergence of \"omic\" technologies has enabled biomarkers to become reliable and accurate predictors of outcomes during cancer treatment.</p><p><strong>Content: </strong>In this review, we highlight the clinical utility of biomarkers in cancer identification and motivate researchers to establish a personalized/precision approach in oncology. By extending a multidisciplinary technology-based approach, biomarkers offer an alternative to traditional techniques, fulfilling the goal of cancer therapeutics to find a needle in a haystack.</p><p><strong>Summary and outlook: </strong>We target different forms of cancer to establish a dynamic role of biomarkers in understanding the spectrum of malignancies and their biochemical and molecular characterization, emphasizing their prospective contribution to cancer screening. Biomarkers offer a promising avenue for the early detection of human cancers and the exploration of novel technologies to predict disease severity, facilitating maximum survival and minimum mortality rates. This review provides a comprehensive overview of the potential of biomarkers in oncology and highlights their prospects in advancing cancer diagnosis and treatment.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"5-20"},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101261","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":"Association of ITPA 94C>A genetic polymorphisms with azathioprine induced adverse effects in the South Indian population.","authors":"Reka Deva, Priyadharsini Rajendran, Sivaranjini Ramasamy, Senthamizh Selvan, Kesavan Ramasamy","doi":"10.1515/dmpt-2023-0061","DOIUrl":"10.1515/dmpt-2023-0061","url":null,"abstract":"<p><strong>Objectives: </strong>Azathioprine (AZA) is an effective immunosuppressant commonly used for malignancy and immune-mediated disorders. The association between genetic polymorphisms and AZA-induced adverse effects has not been elucidated. Hence this study aimed to evaluate the relationship between single nucleotide polymorphisms of ITPA (C94A) with azathioprine-induced adverse effects.</p><p><strong>Methods: </strong>A cross-sectional study was performed on 120 patients who were on AZA therapy for immunobullous disorders and inflammatory bowel disease (IBD). Eligible patients were enrolled from outpatient Departments of dermatology and medical gastroenterology and five mL of blood was collected after obtaining written informed consent. DNA extraction and genotyping were done by phenol-chloroform method and real-time polymerase chain reaction (RT-PCR), respectively.</p><p><strong>Results: </strong>The minor allele frequency of ITPA (A allele) was 30.8 %. The mutant genotypes of ITPA (C94A) were found to have no significant association with overall adverse effects in the South Indian patients on AZA therapy.</p><p><strong>Conclusions: </strong>We report no significant association between ITPA rs1127354 genetic polymorphism and adverse effects in the South Indian patients on AZA therapy.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"21-26"},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801171","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":"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}