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Antineoplastic pharmacokinetics

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https://www.readbyqxmd.com/read/28073144/food-effect-studies-for-oncology-drug-products
#1
Sandeep Parsad, Mark 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 conduced early, and potentially often, during drug development with standardization on how rationale fasting or fed recommendations are presented in the package insert...
January 10, 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
#2
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
#3
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...
December 20, 2016: 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
#4
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
https://www.readbyqxmd.com/read/27908266/is-metformin-a-perfect-drug-updates-in-pharmacokinetics-and-pharmacodynamics
#5
Magdalena Markowicz-Piasecka, Kristiina Maria Huttunen, Łukasz Mateusiak, Elżbieta Mikiciuk-Olasik, Joanna Sikora
Metformin, a synthetic biguanide, is currently one of the most frequently recommended medications for type 2 diabetes treatment around the world. In this review, we present the latest discoveries in the pharmacokinetics of metformin, especially the role of transporters (e.g. Organic Cation Transporters OCTs, Multidrug and Toxin Extrusion transporters MATE) in oral absorption, distribution, elimination and biochemical effects of metformin in humans. We also review the associations between genetic variations of metformin transporters, their pharmacokinetics and drug efficacy or drug responses...
December 1, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27874243/ultra-high-performance-liquid-chromatography-electrospray-ionization-tandem-mass-spectrometry-and-pharmacokinetic-analysis-of-justicidin-b-and-6-hydroxy-justicidin-c-in-rats
#6
Jiaoyang Luo, Yichen Hu, Jia'an Qin, Meihua Yang
Arylnaphthalene lignans have attracted considerable interest with the discovery of their antineoplastic activities. Two such compounds are justicidin B and 6'-hydroxy justicidin C, both of which have been isolated from the herb Justicia procumbens. We sought to develop and validate a sensitive and accurate, ultra high performance liquid chromatography with electrospray ionization tandem mass spectrometry method for the structural determination and pharmacokinetics of justicidin B and 6'-hydroxy justicidin C...
November 22, 2016: Journal of Separation Science
https://www.readbyqxmd.com/read/27793950/phase-i-study-of-the-pan-pi3k-inhibitor-buparlisib-in-adult-chinese-patients-with-advanced-solid-tumors
#7
Yi-Long Wu, L I Zhang, Lucia Trandafir, Tuochuan Dong, Vincent Duval, Katharine Hazell, Binghe Xu
BACKGROUND/AIM: The phosphatidylinositol-3-kinase (PI3K) signaling pathway is frequently activated in cancer. Buparlisib (BKM120), an oral pan-PI3K inhibitor, inhibits proliferation of human cancer in preclinical models. Studies of buparlisib in Western and Japanese adults with advanced solid tumors established a recommended dose of 100 mg/day and showed an acceptable safety profile and evidence of efficacy. This phase I dose-escalation/expansion study aimed to establish the maximum tolerated dose (MTD) of single-agent, once daily oral buparlisib in Chinese patients with advanced solid tumors...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27784242/introduction-for-design-of-nanoparticle-based-drug-delivery-systems
#8
Edgar Chan, Hui Wang
Conventional drug delivery systems contain numerous limitations such as limited targeting, low therapeutic indices, poor water solubility, and the induction of drug resistances. In order to overcome the drawbacks of conventional pathway of drug delivery, nanoparticle delivery systems are therefore designed and used as the drug carriers. Nanoparticle based drug delivery systems have been rapidly growing and are being applied to various sections of biomedicine. Drug nanocarriers based on dendrimers, liposomes, self-assembling peptides, water-soluble polymers, and block copolymer micelles are the most extensively studied types of drug delivery systems and some of them are being used in clinical therapy...
October 25, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27765931/the-natural-compound-sulforaphene-as-a-novel-anticancer-reagent-targeting-pi3k-akt-signaling-pathway-in-lung-cancer
#9
Ming Yang, Haiyong Wang, Mo Zhou, Weilin Liu, Pengqun Kuang, Hao Liang, Qipeng Yuan
Lung cancer is one of the leading causes of cancer death worldwide. Isothiocyanates from cruciferous vegetables been shown to possess anticarcinogenic activities in lung malignances. We previously found sulforaphene (4-methylsufinyl-3-butenyl isothiocyanate, SFE), one new kind of isothiocyanates, existing in a relative high abundance in radish seeds. An efficient methodology based on macroporous resin and preparative high-performance liquid chromatography was developed to isolate SFE in reasonably large quantities, high purity and low cost...
September 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27709238/body-composition-and-anti-neoplastic-treatment-in-adult-and-older-subjects-a-systematic-review
#10
S Gérard, D Bréchemier, A Lefort, S Lozano, G Abellan Van Kan, T Filleron, L Mourey, C Bernard-Marty, M E Rougé-Bugat, V Soler, B Vellas, M Cesari, Y Rolland, L Balardy
BACKGROUND: The estimation of the risk of poor tolerance and overdose of antineoplastic agents protocols represents a major challenge in oncology, particularly in older patients. We hypothesize that age-related modifications of body composition (i.e. increased fat mass and decreased lean mass) may significantly affect tolerance to chemotherapy. METHOD: We conducted a systematic review for the last 25 years (between 1990 and 2015), using US National library of Medicine Medline electronic bibliographic database and Embase database of cohorts or clinical trials exploring (i) the interactions of body composition (assessed by Dual X-ray Absorptiometry, Bioelectrical Impedance Analyses, or Computerized Tomography) with pharmacokinetics parameters, (ii) the tolerance to chemotherapy, and (iii) the consequences of chemotherapies or targeted therapies on body composition...
2016: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/27619395/lanreotide-depot-an-antineoplastic-treatment-of-carcinoid-or-neuroendocrine-tumors
#11
REVIEW
Edward M Wolin, Amandine Manon, Christophe Chassaing, Andy Lewis, Laurent Bertocchi, Joel Richard, Alexandria T Phan
PURPOSE: Peptide drugs for antineoplastic therapies usually have low oral bioavailability and short in vivo half-lives, requiring less preferred delivery methods. Lanreotide depot is a sustained-release somatostatin analog (SSA) formulation produced via an innovative peptide self-assembly method. Lanreotide is approved in the USA and Europe to improve progression-free survival (PFS) in patients with unresectable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and also approved in Europe for symptom control in carcinoid syndrome associated with GEP-NETs...
December 2016: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/27613245/the-effect-of-increased-lipoproteins-levels-on-the-disposition-of-vincristine-in-rat
#12
Hadeel A Khalil, Tarek S Belal, Ahmed F El-Yazbi, Dalia A Hamdy
BACKGROUND: Vincristine (VCR), an antineoplastic agent, is a key component in the treatment of acute lymphoblastic leukemia, lymphomas, rhabdomyosarcoma, neuroblastoma, and Wilms' tumor diseases. Recently, high incidence of hyperlipidemia was reported to be associated with allogenic hematopoietic stem cell transplantation and VCR/L-asparaginase therapy. The aim of this study is to test the effects of incremental increase in lipoproteins levels on vincristine disposition in rat. METHOD: To study VCR pharmacokinetics and protein binding, rats (n = 25) were assigned to three groups, normal lipidemic (NL), intermediate (IHL) and extreme hyperlipidemic (HL)...
September 9, 2016: Lipids in Health and Disease
https://www.readbyqxmd.com/read/27521531/a-novel-approach-for-the-simultaneous-quantification-of-18-small-molecule-kinase-inhibitors-in-human-plasma-a-platform-for-optimised-ki-dosing
#13
Madelé van Dyk, John O Miners, Ganessan Kichenadasse, Ross A McKinnon, Andrew Rowland
Small molecule kinase inhibitors (KIs) are a rapidly expanding class of narrow therapeutic index antineoplastic drugs that exhibit substantial inter-individual variability in exposure. This manuscript describes a novel approach for the quantification of 18 KIs in plasma, providing a platform that is unparalleled in terms of scope for the assessment of KI therapeutic drug monitoring (TDM) and facilitating pharmacokinetic studies with KIs. Following the addition of a panel of four deuterated internal standards, plasma samples were prepared by solvent precipitation with acidified methanol...
October 15, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27455550/bile-salt-liposomes-for-enhanced-lymphatic-transport-and-oral-bioavailability-of-paclitaxel
#14
Bin Zhang, Aiying Xue, Chen Zhang, Jinlong Yu, Wen Chen, Deqing Sun
Paclitaxel (PTX), a BCS class IV drug that is characterized by its poor solubility and is a substrate for P-glycoprotein, is one of the most widely used antineoplastic agents. However, oral administration of PTX for chemotherapy is highly challenging. The aim of this study was to develop bile-salt liposomes (BS-Lips) to enhance the absorption of PTX and thus improve its therapeutic outcome. The BS-Lips were prepared by the thin-film hydration method and characterized in terms of particle size and morphology...
June 2016: Die Pharmazie
https://www.readbyqxmd.com/read/27440490/population-pharmacokinetic-pk-analysis-of-laromustine-an-emerging-alkylating-agent-in-cancer-patients
#15
Ala F Nassar, Adam V Wisnewski, Ivan King
1. Alkylating agents are capable of introducing an alkyl group into nucleophilic sites on DNA or RNA through covalent bond. Laromustine is an active member of a relatively new class of sulfonylhydrazine prodrugs under development as antineoplastic alkylating agents, and displays significant single-agent activity. 2. This is the first report of the population pharmacokinetic analysis of laromustine, 106 patients, 66 with hematologic malignancies and 40 with solid tumors, participated in five clinical trials worldwide...
July 20, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27388491/pharmacokinetics-and-pharmacodynamics-evaluation-of-a-thermosensitive-chitosan-based-hydrogel-containing-liposomal-doxorubicin
#16
Shuangxia Ren, Yu Dai, Cuiyun Li, Zhixia Qiu, Xin Wang, Fengjie Tian, Sufeng Zhou, Qi Liu, Han Xing, Yang Lu, Xijing Chen, Ning Li
In situ gelling thermosensitive hydrogel formulation has been reported to effectively sustain the release of macromolecules for a long time. However, the low-molecular-weight hydrophilic drugs, such as doxorubicin (DOX), are not suitable for intratumoral injection because the release will complete within one day. In this study, liposomal doxorubicin (LipDOX) was added into the hydrogel to form a novel thermosensitive formulation which prolonged the sustained release of DOX. DOX+C/GP (doxorubicin in chitosan/β-glycerophosphate) was prepared to compare with LipDOX+C/GP (liposomal doxorubicin in chitosan/β-glycerophosphate hydrogel)...
September 20, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27278668/pharmacokinetics-and-safety-of-vitamin-e-%C3%AE-tocotrienol-after-single-and-multiple-doses-in-healthy-subjects-with-measurement-of-vitamin-e-metabolites
#17
Amit Mahipal, Jason Klapman, Shivakumar Vignesh, Chung S Yang, Anthony Neuger, Dung-Tsa Chen, Mokenge P Malafa
PURPOSE: Vitamin E delta-tocotrienol (VEDT) has demonstrated chemopreventive and antineoplastic activity in preclinical models. The aim of our study was to determine the safety and pharmacokinetics of VEDT and its metabolites after single- and multiple-dose administrations in healthy subjects. METHODS: Thirty-six subjects received from 100 to 1600 mg of oral VEDT as a single dose or twice daily for 14 consecutive days. A 3 + 3 dose escalation design was utilized...
July 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27235158/cross-validation-of-a-mass-spectrometric-based-method-for-the-therapeutic-drug-monitoring-of-irinotecan-implementation-of-matrix-assisted-laser-desorption-ionization-mass-spectrometry-in-pharmacokinetic-measurements
#18
Eleonora Calandra, Bianca Posocco, Sara Crotti, Elena Marangon, Luciana Giodini, Donato Nitti, Giuseppe Toffoli, Pietro Traldi, Marco Agostini
Irinotecan is a widely used antineoplastic drug, mostly employed for the treatment of colorectal cancer. This drug is a feasible candidate for therapeutic drug monitoring due to the presence of a wide inter-individual variability in the pharmacokinetic and pharmacodynamic parameters. In order to determine the drug concentration during the administration protocol, we developed a quantitative MALDI-MS method using CHCA as MALDI matrix. Here, we demonstrate that MALDI-TOF can be applied in a routine setting for therapeutic drug monitoring in humans offering quick and accurate results...
July 2016: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/27229857/recent-insights-in-nanotechnology-based-drugs-and-formulations-designed-for-effective-anti-cancer-therapy
#19
REVIEW
Ewelina Piktel, Katarzyna Niemirowicz, Marzena Wątek, Tomasz Wollny, Piotr Deptuła, Robert Bucki
The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents...
May 26, 2016: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/27217747/development-and-evaluation-of-vitamin-e-d-%C3%AE-tocopheryl-polyethylene-glycol-1000-succinate-mixed-polymeric-phospholipid-micelles-of-berberine-as-an-anticancer-nanopharmaceutical
#20
Roger Shen, Jane J Kim, Mingyi Yao, Tamer A Elbayoumi
Berberine (Brb) is an active alkaloid occurring in various common plant species, with well-recognized potential for cancer therapy. Brb not only augments the efficacy of antineoplastic chemotherapy and radiotherapy but also exhibits direct antimitotic and proapoptotic actions, along with distinct antiangiogenic and antimetastatic activities in a variety of tumors. Despite its low systemic toxicity, several pharmaceutical challenges limit the application of Brb in cancer therapy (ie, extremely low solubility and permeability, very poor pharmacokinetics (PKs), and oral bioavailability)...
2016: International Journal of Nanomedicine
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