Journal of Drug Metabolism and Toxicology最新文献_第3页

Hazardous Influence of Hydroxyurea on Spermatogenesis in Thalassemia Intermedia Patients: An Egyptian Cohort Study 羟基脲对地中海贫血患者精子发生的危险影响:一项埃及队列研究

Journal of Drug Metabolism and Toxicology Pub Date : 2018-01-01 DOI: 10.4172/2157-7609.1000237

Mohsen Saleh Elalfy, F. Ebeid, Islam Reda Elgamry, Ghada Mamdouh Fawzy, H. Elsedfy, M. Hamza

{"title":"Hazardous Influence of Hydroxyurea on Spermatogenesis in Thalassemia Intermedia Patients: An Egyptian Cohort Study","authors":"Mohsen Saleh Elalfy, F. Ebeid, Islam Reda Elgamry, Ghada Mamdouh Fawzy, H. Elsedfy, M. Hamza","doi":"10.4172/2157-7609.1000237","DOIUrl":"https://doi.org/10.4172/2157-7609.1000237","url":null,"abstract":"Background: Hydroxyurea (HU), frequently used in thalassemia intermedia (TI), might have adverse effects on spermatogenesis. Aim: To assess the effects of HU treatment on sperm parameters and potential reversibility on its discontinuation in TI patients. Methods: Twenty fully-pubertal male TI patients regularly followed-up at the Ain Shams University Thalassemia Center were classified according to previous HU treatment (1:1); first group had received HU for ≥ one year, while the second had never received HU. All recruited patients were subjected to full clinical assessments. Sperm parameters (number, abnormal forms, motility and forward progression) were assessed at enrollment and reassessed six- months after stopping HU treatment. Result: Eleven patients on HU therapy had statistically significant lower sperm count in comparison to those who had never received HU. At six months off HU therapy, there was statistically significant improvement of all sperm parameters. Nevertheless, such parameters were still lower than those of patients who had never received HU. Statistically significant relationships were noted between total sperm count and HU dose, compliance and duration of therapy. Conclusion: HU appears to have a hazardous yet reversible effect on sperm health in pubertal TI patients. Counseling should be offered with close follow-up of its effect on fertility.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"34 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82736728","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}

引用次数: 0

Sublingual Absorption of Naloxone in a Large Clinical Population 纳洛酮在大量临床人群中的舌下吸收

Journal of Drug Metabolism and Toxicology Pub Date : 2018-01-01 DOI: 10.4172/2157-7609.1000240

D. M. Strickland, Jana Burson

{"title":"Sublingual Absorption of Naloxone in a Large Clinical Population","authors":"D. M. Strickland, Jana Burson","doi":"10.4172/2157-7609.1000240","DOIUrl":"https://doi.org/10.4172/2157-7609.1000240","url":null,"abstract":"Background and Objectives: The combination of buprenorphine and naloxone (combo product) is a medication that is administered sublingually to treat opioid use disorder as part of medication assisted treatment. The naloxone component is believed to deter inappropriate use of the medication. True allergies to naloxone are infrequent, but many patients experience severe, unpleasant side effects that they associate with the combo product but not with the formulation containing buprenorphine alone (mono product). It is commonly contended that naloxone is poorly absorbed sublingually, so we sought to test the validity of that belief. Methods: Using a sensitive LC-MS assay, we quantified the concentration of naloxone in the urine of 61 patients (Total specimens=686) prescribed the combo product. Because this study was retrospective it was neither intended nor possible to compare adverse side effects between patients prescribed mono versus combo products. Results: We found that 92.7% of the patients prescribed the combo product had significant quantifiable concentrations of naloxone in their urine drug screens. Conclusions and Scientific Significance: Contrary to popular belief, naloxone is absorbed sublingually. Such absorption may account for some of the unpleasant side effects experienced by patients treated with the combo products, but it was not possible to compare or quantify side effects in this retrospective study. We feel it is important that clinicians be aware of the possibility of significant sublingual absorption of naloxone when choosing therapeutic modalities for their patients.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"28 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75727115","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}

引用次数: 11

Effect of CB1-Antagonist (AM251) on Metabolic Syndrome (Prophylactic and Therapeutic) cb1拮抗剂AM251对代谢综合征的预防和治疗作用

Journal of Drug Metabolism and Toxicology Pub Date : 2018-01-01 DOI: 10.4172/2157-7609.1000236

Haneen Alrawashdeh, Afif Ahmed, L. Madi, A. Ahmed, Dhiaddin Serheed

引用次数: 0

Bioactive Indanes: Comparative in vitro Metabolism Study of PH46A, a New Potential Anti-inflammatory Agent and Biosynthesis of its Primary Metabolite PH132 生物活性吲哚类:新型潜在抗炎药PH46A的体外代谢比较研究及其主要代谢物PH132的生物合成

Journal of Drug Metabolism and Toxicology Pub Date : 2018-01-01 DOI: 10.4172/2157-7609.1000239

Tao Zhang, G. Scalabrino, N. Frankish, H. Sheridan

{"title":"Bioactive Indanes: Comparative in vitro Metabolism Study of PH46A, a New Potential Anti-inflammatory Agent and Biosynthesis of its Primary Metabolite PH132","authors":"Tao Zhang, G. Scalabrino, N. Frankish, H. Sheridan","doi":"10.4172/2157-7609.1000239","DOIUrl":"https://doi.org/10.4172/2157-7609.1000239","url":null,"abstract":"PH46A is the lead of a new class of bioactive indanes with potential for the treatment of inflammatory bowel disease. A qualitative in vitro metabolism profile of PH46A was investigated in preclinical studies, and the rate of its metabolism in cryopreserved hepatocytes prepared from male Sprague Dawley rat, Beagle dog, Cynomolgus monkey and pooled mixed gender human was compared by LC-MS. The clearance order of PH46A was determined to be rat>dog>monkey>human. The species tested which exhibited the closest clearance values to the human was monkey. Following incubation of PH46A with cryopreserved hepatocytes, 5 metabolites were identified, including M1 (keto-PH46), M2 (PH46-OH, PH132), M3 (PH46-diOH), M4 (keto-glucuronide-PH46) and M5 (glucuronide conjugate-PH46). It was found that the human metabolites M2 and M5 were also present in rat, dog and monkey, while M1 was present in all species except monkey. M2 was detected in dog and monkey by LC1 conditions, but only in dog by LC2. Therefore, the metabolism in rat was most similar to human, in terms of the metabolites observed, but all putative human metabolites were present in rat and dog. We further explored the characterization of key metabolite M2 (PH46-OH). Identical PH46-OH was obtained via a bio-catalytic oxidation method from PH46 using rat liver microsomes (RLM) and the human liver P450s (Cyp2D6, Cyp 2C19 and Cyp 4A11) following screening of selectAZyme panels of microbial P450s, recombinant human liver P450s and different microsomes. RLM was used in scale up production and PH132 was isolated and characterized as 4-(((1’S,2’S)-1’,6-dihydroxy-1’,3’-dihydro- 1H,2’H-[2,2’-biinden]-2’-yl)methyl) benzoic acid via LC-MS/MS, NMR and HRMS. The site of hydroxylation on the biindane scaffold was unexpected. The outcomes of these studies have provided valuable information for future pharmacokinetic and in vivo toxicological investigations.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"76 1","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88010604","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}

引用次数: 1

Detection and Identification of Reactive Drug Metabolites Leading to Idiosyncratic Toxicity: Lapatinib as a Case Example 导致特异性毒性的反应性药物代谢物的检测和鉴定:拉帕替尼为例

Journal of Drug Metabolism and Toxicology Pub Date : 2018-01-01 DOI: 10.4172/2157-7609.1000242

Rayane Mohamed, F. Storelli, J. Sidibé, N. Bararpour, J. Desmeules, Marc Ausburger, Y. Daali, Aurélien Thomas

{"title":"Detection and Identification of Reactive Drug Metabolites Leading to Idiosyncratic Toxicity: Lapatinib as a Case Example","authors":"Rayane Mohamed, F. Storelli, J. Sidibé, N. Bararpour, J. Desmeules, Marc Ausburger, Y. Daali, Aurélien Thomas","doi":"10.4172/2157-7609.1000242","DOIUrl":"https://doi.org/10.4172/2157-7609.1000242","url":null,"abstract":"New pharmaceutical drug development requires more than a billion dollars and can take 12 years of research effort. New chemical entities or NCEs can be dropped from development for many reasons during this process, two major reasons being efficacy and toxicity. Lapatinib was approved in 2007 by FDA as an orally active drug against breast cancer. While some advantages were observed over chemotherapy, clinical evidences of idiosyncratic hepatoxicity were reported for this compound. Numerous studies showed that lapatinib was extensively metabolized and the formation of reactive metabolites could be the origin of the observed toxicity. It has been shown that CYP3A are the main drug metabolizing enzymes involved in the metabolism pathway of lapatinib. This study aims to identify and detect potential reactive metabolites of lapatinib formed after in vitro microsomal incubation using a comprehensive workflow for drug metabolism studies. Using micro ultra-high performance liquid chromatography coupled to high resolution mass spectrometry, we were successful to identify a new quinoneiminine reactive metabolite, which upon conjugation with gluthatione (GSH) formed a GSH related product. This product was further characterized by tandem mass spectrometry, using data-dependent and neutral loss scans. This workflow could be successfully applied to other drugs and pharmaceuticals in order to allow the comprehensive mapping of metabolism pathways and the potential identification of reactive species.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"21 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75236949","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}

引用次数: 1

MCR-1 Colistin Resistance in Escherichia coli Wildlife: A Continental Mini-review 野生大肠杆菌MCR-1粘菌素耐药性:大陆迷你综述

Journal of Drug Metabolism and Toxicology Pub Date : 2018-01-01 DOI: 10.4172/2157-7609.1000243

A. A. Shad

引用次数: 5

Metabolism of Drugs with Inhibition of Enzymes 酶抑制药物的代谢

Journal of Drug Metabolism and Toxicology Pub Date : 2018-01-01 DOI: 10.4172/2157-7609.1000233

Varsha Singh, P. Sharma, A. Alam

引用次数: 1

A Mechanism by Which Propofol Induces Cytotoxicity 异丙酚诱导细胞毒性的机制

Journal of Drug Metabolism and Toxicology Pub Date : 2017-09-04 DOI: 10.4172/2157-7609.1000230

S. Onizuka, N. Ikewaki, S. Shiraishi

{"title":"A Mechanism by Which Propofol Induces Cytotoxicity","authors":"S. Onizuka, N. Ikewaki, S. Shiraishi","doi":"10.4172/2157-7609.1000230","DOIUrl":"https://doi.org/10.4172/2157-7609.1000230","url":null,"abstract":"Background: Many studies have reported on the cytotoxicity of propofol; however, the mechanism is still unclear. The aim of this study was to clarify the mechanisms of cytotoxicity induced by propofol. \u0000Methods: Using Hela cells, viability was measured using a calcein-AM assay. Apoptosis was observed by DNA fragmentation, caspase activity. Mitochondrial membrane potential, and mitochondrial pH were measured using the ratiometric fluorescent probes JC-1 and SNARF-1 to clarify the mechanisms of mitochondrial cytotoxicity. \u0000Furthermore, the pH of both the intra- and extra-membrane was measured simultaneously using 5-hexadecanoylaminofluorescein (HAF), a ratiometric pH sensitive fluorescent probe. \u0000Results: Propofol (0~69.6 μM) reduced the viability of Hela cells in a dose- and time-dependent manner. Propofol induced apoptosis through the mitochondrial pathway, induced mitochondrial depolarization. Propofol (10 μM) also resulted in the loss of the pH gradient at cytosol and mitochondria, as did CCCP (10 μM). \u0000Conclusion: Propofol acts as a protonophore, and this chemical property induces apoptosis in cancer cell lines through the mitochondrial pathway by disappearance of the pH gradient.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"12 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2017-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83044746","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}

引用次数: 2

Nanotechnology for combating multi-drug resistance: A next generation antimicrobial therapy 对抗多药耐药的纳米技术:新一代抗菌疗法

Journal of Drug Metabolism and Toxicology Pub Date : 2017-08-10 DOI: 10.4172/2157-7609-C1-009

Tikam Ch, Dakal, Mamta Pal

引用次数: 2

Treatment of Depression in Patients under Breast Cancer Therapy: Antidepressant-Tamoxifen Drug Interactions 乳腺癌患者抑郁症的治疗:抗抑郁药与他莫昔芬药物的相互作用

Journal of Drug Metabolism and Toxicology Pub Date : 2017-05-17 DOI: 10.4172/2157-7609.1000228

C. Aguiar, João Vicente Augusto Aguiar, Marcelo Gondim Rocha

引用次数: 0