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Antineoplastic pharmacokinetics

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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
#1
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
#2
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
#3
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...
November 21, 2017: 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
#4
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...
November 11, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29131861/delivery-of-epirubicin-via-slow-infusion-as-a-strategy-to-mitigate-chemotherapy-induced-cardiotoxicity
#5
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
#6
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...
October 27, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29078726/stereochemical-considerations-in-pharmacokinetic-processes-of-representative-antineoplastic-agents
#7
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
#8
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
https://www.readbyqxmd.com/read/28921641/pharmacokinetic-guided-dosing-of-new-oral-cancer-agents
#9
Catherine J Lucas, Jennifer H Martin
Generally, licensed drug-dosing recommendations for chemotherapy are based on results from clinical trials in which subjects are usually of relatively normal body size, middle-aged, and are relatively racially homogeneous, with minimal comorbidity and specific tumor characteristics. Very few nontrial patients meet these characteristics, resulting in clinical practice having to extrapolate dosing recommendations to the specific patient. There is insufficient research on the impact of obesity-associated physiological changes prevalent in patients with common cancers on standard pharmacokinetic and pharmacodynamic parameters...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28844758/extensive-preclinical-investigation-of-polymersomal-formulation-of-doxorubicin-versus-doxil-mimic-formulation
#10
Mona Alibolandi, Khalil Abnous, Marzieh Mohammadi, Farzin Hadizadeh, Fatemeh Sadeghi, Sahar Taghavi, Mahmoud Reza Jaafari, Mohammad Ramezani
Due to the severe cardiotoxicity of doxorubicin, its usage is limited. This shortcoming could be overcome by modifying pharmacokinetics of the drugs via preparation of various nanoplatforms. Doxil, a well-known FDA-approved nanoplatform of doxorubicin as antineoplastic agent, is frequently used in clinics in order to reduce cardiotoxicity of doxorubicin. Since Doxil shows some shortcomings in clinics including hand and food syndrome and very slow release pattern thus, there is a demand for the development and preparation of new doxorubicin nanoformulation with fewer side effects...
October 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28756607/a-randomized-open-label-two-way-crossover-single-dose-bioequivalence-study-of-temozolomide-200%C3%A2-mg-m-2-dralitem-%C3%A2-vs-temodal-%C3%A2-capsules-in-patients-with-primary-tumors-of-the-central-nervous-system-under-fasting-conditions
#11
Alejandro Muggeri, Miguel Vago, Sebastián Pérez, Marcelo Rubio, Cecilia González, Cristian Magariños, Mónica Rosenberg, Fernando Costa, Santiago Pérez-Lloret
BACKGROUND: Temozolomide is an antineoplastic agent of proven efficacy against high-grade gliomas. PURPOSE: The objective of this crossover, single-dose, bioequivalence study was to compare the rate and extent of absorption of oral temozolomide after administration of the study product (Dralitem(®), Monte Verde Sociedad Anónima) and the reference product (Temodal(®), originator product manufactured by Schering Plough Laboratories) in patients with primary central nervous system (CNS) tumors under fasting conditions...
September 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28754470/oleanane-ursane-and-quinone-methide-friedelane-type-triterpenoid-derivatives-recent-advances-in-cancer-treatment
#12
REVIEW
Jorge A R Salvador, Ana S Leal, Ana S Valdeira, Bruno M F Gonçalves, Daniela P S Alho, Sandra A C Figueiredo, Samuel M Silvestre, Vanessa I S Mendes
Natural pentacyclic triterpenoids (PTs) have been often reported to exhibit a wide range of biological activities. Among them, the anticancer and anti-inflammatory activities are the most studied. Over the last two decades, the number of publications reporting the anticancer effects of PTs has risen exponentially, reflecting the increasing interest in these natural products for the development of new antineoplastic drugs. Among of the most investigated PTs regarding their anticancer properties are oleanane-, ursane and friedelane-types, including oleanolic, glycyrrhetinic, ursolic and asiatic acids, and celastrol, among others...
July 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28680445/validation-of-a-liquid-chromatography-tandem-mass-spectrometric-assay-for-quantitative-analysis-of-lenvatinib-in-human-plasma
#13
Tomoko Ogawa-Morita, Yoshiyuki Sano, Tomoka Okano, Hirofumi Fujii, Makoto Tahara, Masakazu Yamaguchi, Hironobu Minami
Toward conducting clinical pharmacokinetic studies of an antineoplastic agent, lenvatinib, we developed a liquid chromatography-tandem mass spectrometric assay for its quantitative analysis in human plasma. Analyte (lenvatinib) and internal standard (IS, propranolol) in the plasma were extracted by using acetonitrile and chromatographically separated by using a XTerra MS C18 column with 0.2 mL/min flow and mobile phase starting with 0.1% formic acid in water, followed by increasing percentage of acetonitrile...
2017: International Journal of Analytical Chemistry
https://www.readbyqxmd.com/read/28667459/clinical-pharmacokinetics-and-pharmacodynamics-of-panobinostat
#14
REVIEW
Mathilde Van Veggel, Elsbeth Westerman, Paul Hamberg
Histone deacetylase (HDAC) inhibitors cause an increase in acetylation that leads to an increase in DNA transcription and accumulation of different proteins, reducing cell proliferation and inducing cell death. Panobinostat is a first-in-line HDAC inhibitor approved for treating multiple myeloma in combination with bortezomib and dexamethasone. It is a pan-deacetylase inhibitor and therefore inhibits not only HDAC but also other deacetylases. The main mechanism of action of panobinostat is to inhibit HDAC, which causes cell cycle arrest and apoptosis, leading to it being an antineoplastic drug...
June 30, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28641053/the-discovery-and-development-of-romidepsin-for-the-treatment-of-t-cell-lymphoma
#15
REVIEW
Piotr Smolewski, Tadeusz Robak
Romidepsin is a potent and selective inhibitor of histone deacetylases (HDCAi). It is also the only bicyclic inhibitor to undergo clinical assessment and is considered a promising drug for the treatment of T-cell lymphomas. The cellular action of romidepsin results in enhanced histone acetylation, as well as the acetylation of other nuclear or cytoplasmic proteins, influencing cell cycle, apoptosis, and angiogenesis. In phase II studies involving patients with relapsed or refractory of cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL), romidepsin produced overall response rates (ORR) of 34-35% and 25-38%, with complete response (CR) rates of 6% and 15-18%, respectively...
August 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28620280/pathophysiology-of-chemotherapy-induced-peripheral-neuropathy
#16
REVIEW
Hana Starobova, Irina Vetter
Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics. It can lead to detrimental dose reductions and discontinuation of treatment, and severely affects the quality of life of cancer survivors. Clinically, chemotherapy-induced peripheral neuropathy presents as deficits in sensory, motor, and autonomic function which develop in a glove and stocking distribution due to preferential effects on longer axons. The pathophysiological processes are multi-factorial and involve oxidative stress, apoptotic mechanisms, altered calcium homeostasis, axon degeneration and membrane remodeling as well as immune processes and neuroinflammation...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28513132/%C3%AE-amylase-and-redox-responsive-nanoparticles-for-tumor-targeted-drug-delivery
#17
Yihui Li, Hang Hu, Qing Zhou, Yanxiao Ao, Chen Xiao, Jiangling Wan, Ying Wan, Huibi Xu, Zifu Li, Xiangliang Yang
Paclitaxel (PTX) is an effective antineoplastic agent and shows potent antitumor activity against a wide spectrum of cancers. Yet, the wide clinical use of PTX is limited by its poor aqueous solubility and the side effects associated with its current therapeutic formulation. To tackle these obstacles, we report, for the first time, α-amylase- and redox-responsive nanoparticles based on hydroxyethyl starch (HES) for the tumor-targeted delivery of PTX. PTX is conjugated onto HES by a redox-sensitive disulfide bond to form HES-SS-PTX, which was confirmed by results from NMR, high-performance liquid chromatography-mass spectrometry, and Fourier transform infrared spectrometry...
June 7, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28501439/paclitaxel-what-has-been-done-and-the-challenges-remain-ahead
#18
REVIEW
Ezequiel Bernabeu, Maximiliano Cagel, Eduardo Lagomarsino, Marcela Moretton, Diego A Chiappetta
In recent years, the nanotechnology has offered researchers the opportunity to solve the problems caused by the vehicle of the standard and first formulation of paclitaxel (Taxol(®)), while maximizing the proven antineoplastic activity of the drug against many solid tumors. Hence, different types of nanocarriers have been employed to improve the efficacy, safety, physicochemical properties and pharmacokinetic/pharmacodynamic profile of this drug. To date, paclitaxel is the unique drug that is marketed in three different nanoplatforms for its parenteral delivery: polymeric nanoparticles (Abraxane(®)), liposomes (Lipusu(®)), and polymeric micelles (Genexol(®), Nanoxel(®) and Paclical(®))...
June 30, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28429653/clinical-development-of-fenretinide-as-an-antineoplastic-drug-pharmacology-perspectives
#19
REVIEW
Jason P Cooper, C Patrick Reynolds, Hwangeui Cho, Min H Kang
Fenretinide (4-HPR) is a synthetic retinoid that has cytotoxic activity against cancer cells. Despite substantial in vitro cytotoxicity, response rates in early clinical trials with 4-HPR have been less than anticipated, likely due to the low bioavailability of the initial oral capsule formulation. Several clinical studies have shown that the oral capsule formulation at maximum tolerated dose (MTD) achieved <10 µmol/L concentrations in patients. To improve bioavailability of 4-HPR, new oral powder (LYM-X-SORB®, LXS) and intravenous lipid emulsion (ILE) formulations are being tested in early-phase clinical trials...
June 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28418845/preclinical-development-of-g1t38-a-novel-potent-and-selective-inhibitor-of-cyclin-dependent-kinases-4-6-for-use-as-an-oral-antineoplastic-in-patients-with-cdk4-6-sensitive-tumors
#20
John E Bisi, Jessica A Sorrentino, Jamie L Jordan, David D Darr, Patrick J Roberts, Francis X Tavares, Jay C Strum
Inhibition of the p16INK4a/cyclin D/CDK4/6/RB pathway is an effective therapeutic strategy for the treatment of estrogen receptor positive (ER+) breast cancer. Although efficacious, current treatment regimens require a dosing holiday due to severe neutropenia potentially leading to an increased risk of infections, as well as tumor regrowth and emergence of drug resistance. Therefore, a next generation CDK4/6 inhibitor that can inhibit proliferation of CDK4/6-dependent tumors while minimizing neutropenia could reduce both the need for treatment holidays and the risk of inducing drug resistance...
June 27, 2017: Oncotarget
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