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Antineoplastic pharmacokinetics

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https://www.readbyqxmd.com/read/29643994/grape-seed-procyanidin-extract-against-lung-cancer-the-role-of-microrna-106b-bioavailability-and-bioactivity
#1
Bingye Xue, Qing-Yi Lu, Larry Massie, Clifford Qualls, Jenny T Mao
MiR-106b is an oncomir and a potential target for anti-cancer therapy. We hypothesize that grape seed procyanidin extract (GSE) exerts antineoplastic effects on lung cancer through modulations of miR-106b and its downstream target. We found that GSE significantly down-regulated miR-106b in a variety of lung neoplastic cells and increased cyclin-dependent kinase inhibitor 1A ( CDKN1A ) mRNA and protein (p21) levels. Transfection of miR-106b mimics reversed the up-regulations of CDKN1A mRNA and p21, abrogated the GSE induced anti-proliferative and anti-invasive properties in lung cancer cells...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29558725/a-uhplc-ms-ms-based-method-for-the-simultaneous-monitoring-of-eight-antiblastic-drugs-in-plasma-and-urine-of-exposed-healthcare-workers
#2
Viviana Izzo, Bruno Charlier, Elena Bloise, Marine Pingeon, Marianna Romano, Antonietta Finelli, Alfonso Vietri, Valeria Conti, Valentina Manzo, Maria Alfieri, Amelia Filippelli, Fabrizio Dal Piaz
Exposure of healthcare workers to anticancer drugs requires the combined action of environmental and biological monitoring to assess the effective level of exposure to these chemicals, to improve awareness and to avoid adverse health effects on this category of workers. Cancer chemotherapeutic drugs show different mechanisms of action due to diverse chemical structures; consequently, they differ in hydrophobicity, pharmacokinetics and pharmacodynamics. Therefore, the appearance, accumulation and elimination of each of these molecules in body fluids and tissues might be extremely variable; this prompts the need for a rapid and versatile analytical protocol for the biological monitoring of possible exposure of workers involved in the manipulation, administration and disposal of cancer chemotherapeutic drugs...
March 13, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29558225/bioactivity-and-pharmacological-properties-of-%C3%AE-mangostin-from-the-mangosteen-fruit-a-review
#3
Guoqing Chen, Yong Li, Wei Wang, Liping Deng
Introduction Mangosteen as a rare and precious fruit looks like a queen crown, known as "Queen of Fruit". α-Mangostin (α-MG) is the most representative xanthone isolated from the pericarp of mangosteen, possessing extensive biological activities and pharmacological properties, which can be considered as an antineoplastic agent, antioxidant, anti-proliferation and induces apoptosis in various types of human cancer cells, and has protective effect on induced apoptotic damage. Areas covered The bioactivity and pharmacological Properties of α-MG are being actively investigated by various industrial and academic institutions...
March 20, 2018: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/29550915/effect-of-the-active-ingredient-of-kaempferia-parviflora-5-7-dimethoxyflavone-on-the-pharmacokinetics-of-midazolam
#4
Wataru Ochiai, Hiroko Kobayashi, Satoshi Kitaoka, Mayumi Kashiwada, Yuya Koyama, Saho Nakaishi, Tomomi Nagai, Masaki Aburada, Kiyoshi Sugiyama
5,7-Dimethoxyflavone (5,7-DMF), one of the major components of Kaempferia parviflora, has anti-obesity, anti-inflammatory, and antineoplastic effects. On the other hand, in vitro studies have reported that it directly inhibits the drug metabolizing enzyme family cytochrome P450 (CYP) 3As. In this study, its safety was evaluated from a pharmacokinetic point of view, based on daily ingestion of 5,7-DMF. Midazolam, a substrate of CYP3As, was orally administered to mice treated with 5,7-DMF for 10 days, and its pharmacokinetic properties were investigated...
March 17, 2018: Journal of Natural Medicines
https://www.readbyqxmd.com/read/29536134/conflicting-meal-recommendations-for-oral-oncology-drugs-pose-risks-to-patient-care
#5
Guo Yu, Dan-Na Wu, Yan Gong, Guo-Fu Li, Hong-Hao Zhou
PURPOSE: The labeling information, authorized by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), is expected to guide the method of drug administration with reference to meal intake, aiming at ensuring favorable safety profile and achieving optimal drug exposure. However, interactions between meals and a specific oral anticancer medication are complicated in that could be strongly affected by inter-individual variability in pharmacokinetics, meal compositions, and the timing of drug administration with respect to meal intake, which could lead to conflicting meal recommendations between regulatory authorities...
March 13, 2018: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29516505/methadone-against-cancer-lost-in-translation
#6
REVIEW
Dirk Theile, Gerd Mikus
Recently, the opioid analgesic D,L-methadone has gained much attention as a potential antineoplastic compound, considerably triggered through lay press and media. In consequence, physicians and pharmacists are currently confronted with numerous patients willing to use D,L-methadone against their malignancies. Well-performed in vitro and in vivo models have in fact shown pro-apoptotic effects of D,L-methadone or other opioids, but also proliferation-stimulating properties. Moreover, the mechanisms of proposed opioid-stimulated apoptosis are incompletely described or contradicting...
March 8, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29506228/sarcopenic-obesity-hidden-muscle-wasting-and-its-impact-for-survival-and-complications-of-cancer-therapy
#7
V E Baracos, L Arribas
Body composition, defined as the proportions and distribution of lean and fat tissues in the human body, is an emergent theme in clinical oncology. Severe muscle depletion (sarcopenia) is most easily overlooked in obese patients; the advent of secondary analysis of oncologic images provides a precise and specific assessment of sarcopenia. Here, we review the definitions, prevalence and clinical implications of sarcopenic obesity (SO) in medical and surgical oncology. Reported prevalence of SO varies due to the heterogeneity in the definitions and the variability in the cut points used to define low muscle mass and high fat mass...
February 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29497292/poly-lactic-co-glycolic-acid-loaded-nanoparticles-of-betulinic-acid-for-improved-treatment-of-hepatic-cancer-characterization-in-vitro-and-in-vivo-evaluations
#8
Pranesh Kumar, Ashok K Singh, Vinit Raj, Amit Rai, Amit K Keshari, Dinesh Kumar, Biswanath Maity, Anand Prakash, Sabyasachi Maiti, Sudipta Saha
Purpose: The application of betulinic acid (B), a potent antineoplastic agent, is limited due to poor bioavailability, short plasma half-life and inappropriate tissue distribution. Thus, we aimed to prepare novel 50:50 poly(lactic- co -glycolic acid) (PLGA)-loaded B nanoparticles (BNP) and to compare its anti-hepatocellular carcinoma (HCC) activity with parent B. Methods: BNP were synthesized and characterized using different methods such as scanning electron microscopy (SEM), fourier-transform infrared (FTIR) spectrometry and particle size analyses...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29451684/intracellular-pharmacokinetics-of-gemcitabine-its-deaminated-metabolite-2-2-difluorodeoxyuridine-and-their-nucleotides
#9
Ellen J B Derissen, Alwin D R Huitema, Hilde Rosing, Jan H M Schellens, Jos H Beijnen
AIMS: Gemcitabine (2',2'-difluoro-2'-deoxycytidine, dFdC) is a prodrug that has to be phosphorylated within the tumour cell to become active. Intracellularly formed gemcitabine diphosphate (dFdCDP) and triphosphate (dFdCTP) are held responsible for the antineoplastic effects. However, a major part of gemcitabine is converted into 2',2'-difluoro-2'-deoxyuridine (dFdU) by deamination. In the cell, dFdU can also be phosphorylated to its monophosphate (dFdUMP), diphosphate (dFdUDP) and triphosphate (dFdUTP)...
February 16, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29414017/a-validated-inductively-coupled-plasma-mass-spectrometry-icp-ms-method-for-the-quantification-of-total-platinum-content-in-plasma-plasma-ultrafiltrate-urine-and-peritoneal-fluid
#10
Lieselotte Lemoine, Elsy Thijssen, Jean-Paul Noben, Peter Adriaensens, Robert Carleer, Kurt Van der Speeten
Oxaliplatin is a platinum (Pt)1 containing antineoplastic agent that is applied in current clinical practice for the treatment of colon and appendiceal neoplasms. A fully validated, highly sensitive, high throughput inductively coupled plasma mass spectrometry (ICP-MS) method is provided to quantify the total Pt content in plasma, plasma ultrafiltrate, urine and peritoneal fluid. In this ICP-MS approach, the only step of sample preparation is a 1000-fold dilution in 0.5% nitric acid, allowing the analysis of 17 samples per hour...
January 29, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29361511/outcome-of-490-desensitizations-to-chemotherapy-drugs-with-a-rapid-one-solution-protocol
#11
Eva Pérez-Rodríguez, Juan Antonio Martínez-Tadeo, Natalia Pérez-Rodríguez, Guacimara Hernández-Santana, Ariel Callero-Viera, Elena Rodríguez-Plata, José Carlos García-Robaina
BACKGROUND: Hypersensitivity reactions to chemotherapy drugs are quite frequent. Desensitization for chemotherapy drugs has become an option to maintain first-line therapy in patients who have suffered such reactions. OBJECTIVE: The objective of this study was to describe our experience in desensitization with antineoplastic agents using a rapid 1-solution protocol. METHODS: We performed a 3-year prospective observational study recording all patients who were desensitized with this protocol...
January 17, 2018: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/29273096/genetic-variation-in-human-drug-related-genes
#12
Charlotta Pauline Irmgard Schärfe, Roman Tremmel, Matthias Schwab, Oliver Kohlbacher, Debora Susan Marks
BACKGROUND: Variability in drug efficacy and adverse effects are observed in clinical practice. While the extent of genetic variability in classic pharmacokinetic genes is rather well understood, the role of genetic variation in drug targets is typically less studied. METHODS: Based on 60,706 human exomes from the ExAC dataset, we performed an in-depth computational analysis of the prevalence of functional variants in 806 drug-related genes, including 628 known drug targets...
December 22, 2017: Genome Medicine
https://www.readbyqxmd.com/read/29209521/management-of-patients-with-end-stage-renal-disease-undergoing-chemotherapy-recommendations-of-the-associazione-italiana-di-oncologia-medica-aiom-and-the-societ%C3%A3-italiana-di-nefrologia-sin
#13
Paolo Pedrazzoli, Nicola Silvestris, Antonio Santoro, Simona Secondino, Oronzo Brunetti, Vito Longo, Elena Mancini, Sara Mariucci, Teresa Rampino, Sara Delfanti, Silvia Brugnatelli, Saverio Cinieri
Background: The overall risk of some cancers is increased in patients receiving regular dialysis treatment due to chronic oxidative stress, a weakened immune system and enhanced genomic damage. These patients could benefit from the same antineoplastic treatment delivered to patients with normal renal function, but a better risk/benefit ratio could be achieved by establishing specific guidelines. Key considerations are which chemotherapeutic agent to use, adjustment of dosages and timing of dialysis in relation to the administration of chemotherapy...
2017: ESMO Open
https://www.readbyqxmd.com/read/29197167/to-take-or-not-to-take-with-meals-unraveling-issues-related-to-food-effects-labeling-for-oral-antineoplastic-drugs
#14
Jiexin Deng, Satjit S Brar, Lawrence J Lesko
There has been controversy regarding whether bioavailability of certain oral oncology drugs should be maximized by taking these medications with food, irrespective of label instructions in the dosing and administration section. To provide insight into this controversy, we conducted an in-depth analysis for oral antineoplastic drugs approved by the Food and Drug Administration in 2000-2016 and identified important issues influencing food labeling decisions. Furthermore, a case study involving sonidegib, a drug approved for locally advanced basal cell carcinoma with a significant food effect on exposure, was used to demonstrate the consequences of failure to adhere to food label recommendations using drug-specific population pharmacokinetic and exposure-toxicity models...
December 2, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29161913/development-and-optimization-of-locust-bean-gum-and-sodium-alginate-interpenetrating-polymeric-network-of-capecitabine
#15
Mansi Upadhyay, Sandeep Kumar Reddy Adena, Harsh Vardhan, Sureshwar Pandey, Brahmeshwar Mishra
OBJECTIVE: The objective of the study was to develop interpenetrating polymeric network (IPN) of capecitabine (CAP) using natural polymers locust bean gum (LBG) and sodium alginate (NaAlg). SIGNIFICANCE: The IPN microbeads were optimized by Box-Behnken Design (BBD) to provide anticipated particle size with good drug entrapment efficiency. The comparative dissolution profile of IPN microbeads of CAP with the marketed preparation proved an excellent sustained drug delivery vehicle...
March 2018: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29138046/novel-cremochylomicrons-for-improved-oral-bioavailability-of-the-antineoplastic-phytomedicine-berberine-chloride-optimization-and-pharmacokinetics
#16
Manal A Elsheikh, Yosra S R Elnaggar, Dalia A Hamdy, Ossama Y Abdallah
Berberine chloride (BER) is an antineoplastic phytomedicine that combat non-Hodgkin lymphoma. BER suffers from low oral bioavailability due to p-glycoprotein efflux and first-pass metabolism. Lymphatic drug targeting recently gained a profound attention due to circumventing hepatic first-pass metabolism and targeting lymph diseases. Therefore, novel BER-loaded cremochylomicrons were elaborated to mitigate BER drawbacks and enhance its lymphatic targeting and bioavailability. Optimized cremochylomicron was prepared with 2...
January 15, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29131861/delivery-of-epirubicin-via-slow-infusion-as-a-strategy-to-mitigate-chemotherapy-induced-cardiotoxicity
#17
Fang Yang, Qiao Lei, Lu Li, Jian Chang He, Jiajia Zeng, Chunxiang Luo, Sai-Ching Jim Yeung, Runxiang Yang
BACKGROUND: Continuous infusion of doxorubicin has been a strategy to reduce cardiotoxicity. Epirubicin is another anthracycline in common clinical use. However, evidence is lacking regarding whether this strategy can reduce cardiotoxicity of epirubicin without compromising antineoplastic efficacy. DESIGN AND METHODS: Healthy rats were randomized into groups: epirubicin (8 mg/kg) delivered intraperitoneally via micro osmotic pumps (MOP), epirubicin (8 mg/kg) by intraperitoneal (IP) bolus injection, and placebo control...
2017: PloS One
https://www.readbyqxmd.com/read/29079968/prediction-of-drug-drug-interaction-potential-using-physiologically-based-pharmacokinetic-modeling
#18
REVIEW
Jee Sun Min, Soo Kyung Bae
The occurrence of drug-drug interactions (DDIs) can significantly affect the safety of a patient, and thus assessing DDI risk is important. Recently, physiologically based pharmacokinetic (PBPK) modeling has been increasingly used to predict DDI potential. Here, we present a PBPK modeling concept and strategy. We also surveyed PBPK-related articles about the prediction of DDI potential in humans published up to October 10, 2017. We identified 107 articles, including 105 drugs that fit our criteria, with a gradual increase in the number of articles per year...
December 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29078726/stereochemical-considerations-in-pharmacokinetic-processes-of-representative-antineoplastic-agents
#19
Jing Gu, Zheng Sui, Chunshu Fang, Qunyou Tan
The vast majority of chemical drugs or drug candidates contain stereocenter(s) in their molecular structures. In these molecules, stereochemical properties are vital properties that influence or even determine their drug actions. Therefore, studying the stereochemical issues of drugs (or drug candidates) is necessary for rational drug use. These stereochemical issues are usually involved with the stereoselectivity in pharmacokinetic processes, especially in the metabolism process. Thus, the investigation of the stereochemical issues in drug metabolism process deserves great attention, especially in those chiral/prochiral antineoplastic agents exhibiting pharmacodynamics and toxicologic differences between stereoisomers...
October 27, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28930444/potential-of-phenylbutyrate-as-adjuvant-chemotherapy-an-overview-of-cellular-and-molecular-anticancer-mechanisms
#20
REVIEW
Maha S Al-Keilani, Nour A Al-Sawalha
Despite the advancement in cancer therapy, a high number of patients fail treatment because of drug resistance. Several preclinical in vitro data suggest that phenylbutyrate has antiproliferative, antiangiogenic, antimetastatic, immunomodulatory, and differentiating properties. Moreover, phenylbutyrate administration in vivo provided an oncoprotective effect. However, the results of clinical trials indicate that the antineoplastic potential of phenylbutyrate is hindered by its pharmacokinetic and pharmacodynamic properties...
October 16, 2017: Chemical Research in Toxicology
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