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Antineoplastic pharmacokinetics

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
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
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...
September 13, 2016: Journal of Gastrointestinal Cancer
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)...
2016: Lipids in Health and Disease
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
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
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
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
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
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
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...
2016: Journal of Nanobiotechnology
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
Krystyna M Wozniak, James J Vornov, Ying Wu, Kenichi Nomoto, Bruce A Littlefield, Christopher DesJardins, Yanke Yu, George Lai, Larisa Reyderman, Nancy Wong, Barbara S Slusher
Chemotherapy-induced peripheral neuropathy is a dose-limiting side effect of many antineoplastic agents, but the mechanisms underlying the toxicities are unclear. At their MTDs, the microtubule-binding drugs paclitaxel and ixabepilone induce more severe neuropathy in mice relative to eribulin mesylate, paralleling their toxicity profiles in clinic. We hypothesized that the severity of their neurotoxic effects might be explained by the levels at which they accumulate in the peripheral nervous system. To test this hypothesis, we compared their pharmacokinetics and distribution in peripheral nerve tissue...
June 1, 2016: Cancer Research
Ali Aboel Dahab, Dhia El-Hag, Gamal M Moutamed, Sarah Aboel Dahab, Ramadan Abuknesha, Norman W Smith
PURPOSE: In cancer patients, pharmacokinetic variations between individuals and within individuals due to impairments in organs' function and other reasons such as genetic polymorphisms represent a major problem in disease management, which can result in unpredictable toxicity and variable antineoplastic effects. Addressing pharmacokinetic variations in cancer patients with liver dysfunction and their implications on anticancer and analgesic drugs, in addition to the use of advanced analytical techniques such as metabolomics and pharmacometabolomics, to monitor altered kinetic and discover metabolic biomarkers during therapeutic intervention will help in understanding and reducing pharmacokinetic variations of drugs in cancer patients as a step forward towards personalised medicine...
September 2016: Cancer Chemotherapy and Pharmacology
Go Kimura, Junji Yonese, Takashi Fukagai, Tomomi Kamba, Kazuo Nishimura, Masahiro Nozawa, Hank Mansbach, Ad Theeuwes, Tomasz M Beer, Bertrand Tombal, Takeshi Ueda
OBJECTIVES: To evaluate the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients. METHODS: This was a post-hoc analysis of the phase 3, double-blind, placebo-controlled PREVAIL trial. Asymptomatic or mildly symptomatic chemotherapy-naïve patients with metastatic castration-resistant prostate cancer progressing on androgen deprivation therapy were randomized one-to-one to 160 mg/day oral enzalutamide or placebo until discontinuation on radiographic progression or skeletal-related event and initiation of subsequent antineoplastic therapy...
May 2016: International Journal of Urology: Official Journal of the Japanese Urological Association
Alfonso Toro-Córdova, Fabricio Ledezma-Gallegos, Laura Mondragon-Fuentes, Rafael Jurado, Luis A Medina, Jazmin M Pérez-Rojas, Patricia Garcia-Lopez
Liposomes have been employed as carriers for antineoplastic drugs to improve delivery. We describe an HPLC-UV method for determining cisplatin levels in liposomal and biological samples, which represents an attractive alternative to the widely used flame atomic absorption spectroscopy. Liposomal cisplatin was extracted from liposomes, plasma and tissue samples by using acetonitrile and separated on a Symmetry C18 column. The mobile phase was a mixture of water, methanol and acetonitrile, and detection was performed at 254 nm...
July 2016: Journal of Chromatographic Science
G I Gafton, K Yu Senchik, V G Petrov, V V Semiglazov, N V Tatyanicheva, V G Bespalov, Yu V Semiletova, I G Gafton, G V Zinoviev, G S Kireeva
The study of pharmacokinetics of melphalan in the perfusate and blood plasma during isolated limb regional perfusion (ILRP) was carried out in patients with melanoma (n=21) and soft tissue sarcoma (n = 24). Melphalan was administered as 10 mg/l for a lower extremity and 13 mg/l for a upper extremity. Quantification of melphalan in perfusate and blood samples was performed by means of liquid chromatography/tandem mass spectrometry. 30 samples of the perfusate and 27 venous blood samples were analyzed. During the first 5 minutes of ILRP concentration of melphalan in the perfusate decreased to 13...
2015: Voprosy Onkologii
(no author information available yet)
Surgery is the mainstay of treatment for medullary thyroid cancer. Cytotoxic chemotherapy is generally ineffective in patients with progressive, inoperable, advanced-stage or metastatic tumours. Vandetanib is also authorised in this setting, but it has more harms than benefits. Cabozantinib, like vandetanib, inhibits several tyrosine kinases involved in angiogenesis. Cabozantinib has been authorised in the European Union for use in this setting. In a randomised, placebo-controlled trial in 330 patients, adding cabozantinib to tailored symptomatic treatment did not prolong survival or improve symptoms, despite a favourable effect on tumour imaging and certain laboratory parameters...
January 2016: Prescrire International
Abdullah A Al-Badr, Mansour M Alodhaib
Dacarbazine is a cell cycle nonspecific antineoplastic alkylating agent used in the treatment of metastatic malignant melanoma. This chapter contains the descriptions of the drug: nomenclature, formulae, chemical structure, elemental composition, and appearance. The uses and applications of dacarbazine and the methods that were used for its preparation are reported. The methods which were used for the physical characterization of the drug are ionization constant, solubility, X-ray powder diffraction pattern, crystal structure, melting point, and differential scanning calorimetry...
2016: Profiles of Drug Substances, Excipients, and related Methodology
Johanna Weiss, Thomas Gajek, Bruno Christian Köhler, Walter Emil Haefeli
Venetoclax (ABT-199) represents a specific B-cell lymphoma 2 (Bcl-2) inhibitor that is currently under development for the treatment of lymphoid malignancies. So far, there is no published information on its interaction potential with important drug metabolizing enzymes and drug transporters, or its efficacy in multidrug resistant (MDR) cells. We therefore scrutinized its drug-drug interaction potential in vitro. Inhibition of cytochrome P450 enzymes (CYPs) was quantified by commercial kits. Inhibition of drug transporters (P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP), and organic anion transporting polypeptides (OATPs)) was evaluated by the use of fluorescent probe substrates...
2016: Pharmaceutics
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