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Antineoplastic pharmacokinetics

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https://www.readbyqxmd.com/read/28930444/potential-of-phenylbutyrate-as-adjuvant-chemotherapy-an-overview-of-cellular-and-molecular-anticancer-mechanisms
#1
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 3, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28921641/pharmacokinetic-guided-dosing-of-new-oral-cancer-agents
#2
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
#3
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
#4
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...
July 29, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28210799/dynamic-contrast-enhanced-mr-imaging-pharmacokinetic-parameters-as-predictors-of-treatment-response-of-brain-metastases-in-patients-with-lung-cancer
#14
Grégory Kuchcinski, Emilie Le Rhun, Alexis B Cortot, Elodie Drumez, Romain Duhal, Maxime Lalisse, Julien Dumont, Renaud Lopes, Jean-Pierre Pruvo, Xavier Leclerc, Christine Delmaire
OBJECTIVES: To determine the diagnostic accuracy of pharmacokinetic parameters measured by dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in predicting the response of brain metastases to antineoplastic therapy in patients with lung cancer. METHODS: Forty-four consecutive patients with lung cancer, harbouring 123 newly diagnosed brain metastases prospectively underwent conventional 3-T MRI at baseline (within 1 month before treatment), during the early (7-10 weeks) and midterm (5-7 months) post-treatment period...
September 2017: European Radiology
https://www.readbyqxmd.com/read/28205290/development-and-qualification-of-an-lc-ms-ms-method-for-investigating-the-biological-implications-of-micelle-entrapped-paclitaxel-in-cell-culture-and-rats
#15
Amal Kaddoumi, Kanwaldeep K Gill, Khaled Elfakhri, Sami Nazzal
Paclitaxel is a front-line antineoplastic drug used in chemotherapeutic modalities for treatment of various types of malignancies. However, its efficacy is limited by dose-related toxicities. In this study, we have explored two important biological aspects of entrapping paclitaxel in PEG2000 -DSPE micelles. First, we evaluated the impact of this micellar delivery system on P-glycoprotein (P-gp)-paclitaxel interaction, and we investigated differences in plasma pharmacokinetics of free and micelle-entrapped paclitaxel...
September 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28134229/-interaction-of-oral-form-anticancer-drugs-with-grapefruit-juice
#16
REVIEW
Magdalena Cholewka-Stafińska, Renata Polaniak, Marek Kardas, Mateusz Grajek, Elżbieta Grochowska-Niedworok
Oral medication (tablets, capsules, suspensions, liquids, etc.) are frequently used in therapy. This may arise due to the fact that oral medication patient can take at home and it reduce the stress associated with taking the drug. On the Polish pharmaceutical market can be observed more frequent registration to trading anticancer drugs in oral form. Is also growing interest about drug interactions with food, but they are still less accented than drug-drug interactions. The results of pharmacokinetic studies on the interaction of drugs used in antineoplastic therapy with food are particularly important because of the characteristics of cancer patients, and a growing number of people suffering from cancer and which may have a problem...
January 23, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28073144/food-effect-studies-for-oncology-drug-products
#17
REVIEW
S Parsad, M J Ratain
Oral antineoplastic agents provide convenience to the patient, but are accompanied by challenges distinct from parenteral cancer treatment. Challenges include a more complex pharmacokinetic profile, with food influencing the absorption of many agents. Standards for evaluating and labeling prandial implications on oral chemotherapy are inconsistent; studies to determine food effects should be conducted early, and potentially often, during drug development with standardization on how rational fasting or fed recommendations are presented in the package insert (PI)...
May 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28070894/a-phase-1-open-label-randomized-crossover-study-evaluating-the-bioavailability-of-tas-102-trifluridine-tipiracil-tablets-relative-to-an-oral-solution-containing-equivalent-amounts-of-trifluridine-and-tipiracil
#18
Carlos R Becerra, Kenichiro Yoshida, Hirokazu Mizuguchi, Manish Patel, Daniel Von Hoff
TAS-102 (trifluridine/tipiracil) is composed of an antineoplastic thymidine-based nucleoside analogue trifluridine (FTD), and a thymidine phosphorylase inhibitor, tipiracil (TPI), at a molar ratio of 1:0.5 (weight ratio, 1:0.471). A phase 1 study evaluated relative bioavailability of TAS-102 tablets compared with an oral solution containing equivalent amounts of FTD and TPI. In an open-label, 2-sequence, 3-period, crossover bioavailability study (part 1), patients 18 years or older with advanced solid tumors were randomized to receive TAS-102 tablets (60 mg; 3 × 20-mg tablets) on day 1 and TAS-102 oral solution (60 mg) on days 8 and 15, or the opposite sequence...
January 9, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27999009/use-of-a-physiologically-based-pharmacokinetic-model-to-simulate-drug-drug-interactions-between-antineoplastic-and-antiretroviral-drugs
#19
José Moltó, Rajith Rajoli, David Back, Marta Valle, Cristina Miranda, Andrew Owen, Bonaventura Clotet, Marco Siccardi
Background: Co-administration of antineoplastics with ART is challenging due to potential drug-drug interactions (DDIs). However, trials specifically assessing such DDIs are lacking. Our objective was to simulate DDIs between the antineoplastics erlotinib and gefitinib with key antiretroviral drugs and to predict dose adjustments using a physiologically based pharmacokinetic (PBPK) model. Methods: In vitro data describing chemical properties and pharmacokinetic processes of each drug and their effect on cytochrome P450 isoforms were obtained from the literature...
March 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27960424/new-insight-into-a-cancer-theranostic-probe-efficient-cell-specific-delivery-of-sn-38-guided-by-biotinylated-poly-vinyl-alcohol
#20
Debabrata Dutta, Susan M Alex, Kondapa Naidu Bobba, Kaustabh Kumar Maiti, Sankarprasad Bhuniya
An optically modulated "turn-on" theranostic prodrug TP1 has been explored and formulated with biotinylated poly(vinyl alcohol) (biotinPVA) to obtain desired pharmacokinetics. TP1, consisting of the antineoplastic camptothecin analogue SN-38, and the fluorescent dye rhodol green have been covalently conjugated through a disulfide bond. Glutathione triggering the release of drug and fluorophore has been well established by UV-vis measurements through mass spectral analysis in physiological conditions. The biocompatible biotinPVA formulated prodrug (PTP1) showed remarkably higher stability against blood serum and cell-specific activation in contrast to that of TP1...
December 14, 2016: ACS Applied Materials & Interfaces
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