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Pharmacokinetic, therapeutic drug monitoring, cancer

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https://www.readbyqxmd.com/read/28634655/effect-of-adherence-on-pharmacokinetic-pharmacodynamic-relationships-of-oral-targeted-anticancer-drugs
#1
Evelina Cardoso, Chantal Csajka, Marie P Schneider, Nicolas Widmer
The emergence of oral targeted anticancer agents transformed several cancers into chronic conditions with a need for long-term oral treatment. Although cancer is a life-threatening condition, oncology medication adherence-the extent to which a patient follows the drug regimen that is intended by the prescriber-can be suboptimal in the long term, as in any other chronic disease. Poor adherence can impact negatively on clinical outcomes, notably because most of these drugs are given as a standard non-individualized dosage despite marked inter-individual variabilities that can lead to toxic or inefficacious drug concentrations...
June 20, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28578404/a-simple-and-rapid-lc-ms-ms-method-for-therapeutic-drug-monitoring-of-cetuximab-a-gpco-unicancer-proof-of-concept-study-in-head-and-neck-cancer-patients
#2
François Becher, Joseph Ciccolini, Diane-Charlotte Imbs, Clémence Marin, Claire Fournel, Charlotte Dupuis, Nicolas Fakhry, Bertrand Pourroy, Aurélie Ghettas, Alain Pruvost, Christophe Junot, Florence Duffaud, Bruno Lacarelle, Sebastien Salas
Administration of first-in-class anti-EGFR monoclonal antibody cetuximab is contingent upon extensive pharmacogenomic testing. However in addition to tumor genomics, drug exposure levels could play a critical, yet largely underestimated role, because several reports have demonstrated that cetuximab pharmacokinetic parameters, in particular clearance values, were associated with survival in patients. Here, we have developed an original bioanalytical method based upon the use of LC-MS/MS technology and a simplified sample preparation procedure to assay cetuximab in plasma samples from patients, thus meeting the requirements of standard Therapeutic Drug Monitoring in routine clinical practice...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28555688/a-high-throughput-immunoassay-for-the-therapeutic-drug-monitoring-of-tegafur
#3
Marta Broto, Rita McCabe, Roger Galve, M-Pilar Marco
Cancer is a group of diseases in which abnormal cells grow and divide without control, with the potential to invade other parts of the body. Chemotherapy is a type of treatment that uses chemical agents to treat cancer. These drugs are toxic and produce undesirable adverse drug reactions due to their narrow therapeutic window and highly variable pharmacokinetics, thus, they need to be monitored to establish personalized treatment to achieve maximal efficiency and reduce drug toxicity. Nowadays, therapeutic drug monitoring (TDM) is not routinely used for chemotherapy agents, however, TDM has the potential to improve the clinical benefit of chemotherapy drugs...
May 30, 2017: Analyst
https://www.readbyqxmd.com/read/28540639/exploiting-pharmacokinetic-models-of-tamoxifen-and-endoxifen-to-identify-factors-causing-subtherapeutic-concentrations-in-breast-cancer-patients
#4
Lena Klopp-Schulze, Markus Joerger, Sebastian G Wicha, Rob Ter Heine, Chantal Csajka, Zinnia P Parra-Guillen, Charlotte Kloft
BACKGROUND AND OBJECTIVES: A better understanding of the highly variable pharmacokinetics (PK) of tamoxifen and its active metabolite endoxifen in breast cancer patients is crucial to support individualised treatment. This study used a modelling and simulation approach to quantitatively assess the influence of cytochrome P450 (CYP) 2D6 activity and other relevant factors on tamoxifen and endoxifen PK to identify subgroups at risk for subtherapeutic endoxifen concentrations. METHODS: Simulations were performed using two previously published PK models jointly describing tamoxifen and endoxifen with CYP2D6 and CYP3A4/5 enzyme activities implemented as covariates...
May 24, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28516432/measurement-of-piperacillin-plasma-concentrations-in-cancer-patients-with-suspected-infection
#5
Tobias Rachow, Verena Schlüter, Sibylle Bremer-Streck, Udo Lindig, Sebastian Scholl, Peter Schlattmann, Michael Kiehntopf, Andreas Hochhaus, Marie von Lilienfeld-Toal
BACKGROUND: Piperacillin (PIP) in combination with tazobactam is commonly used for anti-infective treatment in cancer patients. PIP exerts a time-dependent killing. Thus, the maintenance of plasma concentrations above a pre-defined target concentration for a pre-defined time may be relevant for optimal efficacy. It is assumed that PIP-plasma concentrations above the clinical breakpoint of the target pathogen [Pseudomonas aeruginosa, clinical breakpoint at minimal inhibitory concentration (MIC) 16 mg/L] should be reached for 100% of the dosing interval or >4xMIC (64 mg/L) for 50% of the dosing interval...
May 17, 2017: Infection
https://www.readbyqxmd.com/read/28507111/real-life-assessment-of-the-safety-and-effectiveness-of-the-new-tablet-and-intravenous-formulations-of-posaconazole-in-the-prophylaxis-of-invasive-fungal-infections-analysis-of-343-courses
#6
Frank P Tverdek, Sang Taek Heo, Samuel L Aitken, Bruno Granwehr, Dimitrios P Kontoyiannis
BACKGROUND: Posaconazole is the preferred mold-active azole for prophylaxis against invasive fungal infection (IFI) in patients with hematologic malignancy (HM). Delayed release tablet and intravenous formulations of posaconazole have recently become available, but clinical data are limited. We sought to examine the real-world pharmacokinetics and prophylactic effectiveness of the new formulations of posaconazole given as prophylaxis in patients with HM. METHODS: A retrospective cohort of all consecutive adult inpatients with HM who received ≥3 days of posaconazole as tablet or intravenous from 12/1/2013-12/31/2015 for primary IFI prophylaxis at MD Anderson Cancer center...
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28444958/role-of-cytochrome-p450-3a4-and-1a2-phenotyping-in-patients-with-advanced-non-small-cell-lung-cancer-nsclc-receiving-erlotinib-treatment
#7
Zinnia P Parra-Guillen, Peter B Berger, Manuel Haschke, Massimiliano Donzelli, Daria Winogradova, Bogumila Pfister, Martin Früh, Charlotte Kloft, Stephan Krähenbühl, Silke Gillessen, Markus Joerger
Erlotinib is metabolized by cytochrome p450 (CYP) 3A and CYP1A. This study assessed CYP3A4 (midazolam) and CYP1A2 (caffeine) phenotyping in plasma and dried blood spots (DBS) for predicting the pharmacokinetics and toxicity of erlotinib in 36 patients with advanced NSCLC. On day 1, erlotinib 150 mg OD. was initiated, and the 2 oral probe drugs midazolam (2mg) and caffeine (100mg) were added on day 1. Plasma and DBS were collected for erlotinib, OSI-420 and probe drugs for up to 6 hr on day 1 and 2-weekly up to week 10...
April 26, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28346313/population-pharmacokinetics-of-gemcitabine-and-dfdu-in-pancreatic-cancer-patients-using-an-optimal-design-sparse-sampling-approach
#8
Cindy Serdjebi, Florence Gattacceca, Jean-François Seitz, Francine Fein, Johan Gagnière, Eric François, Abakar Abakar-Mahamat, Gael Deplanque, Madani Rachid, Bruno Lacarelle, Joseph Ciccolini, Laetitia Dahan
BACKGROUND: Gemcitabine remains a pillar in pancreatic cancer treatment. However, toxicities are frequently observed. Dose adjustment based on therapeutic drug monitoring might help decrease the occurrence of toxicities. In this context, this work aims at describing the pharmacokinetics (PK) of gemcitabine and its metabolite dFdU in pancreatic cancer patients and at identifying the main sources of their PK variability using a population PK approach, despite a sparse sampled-population and heterogeneous administration and sampling protocols...
June 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28266269/liposomal-nanotechnology-for-cancer-theranostics
#9
Zhifei Dai, Xiuli Yue
Liposomes are a type of biomimetic nanoparticles generated from self-assembling concentric lipid bilayer enclosing an aqueous core domain. They have been attractive nanocarriers for the delivery of many drugs (e.g. radiopharmaceuticals, chemotherapeutic agents, porphyrin) and diagnostic agents (e.g. fluorescent dyes, quantum dots, Gadolinium complex and Fe3O4) by encapsulating (or adsorbing) hydrophilic one inside the liposomal aqueous core domain (or on the bilayer membrane surface), and by entrapping hydrophobic one within the liposomal bilayer...
March 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28183252/pharmacological-profile-and-pharmacogenomics-of-anti-cancer-drugs-used-for-targeted-therapy
#10
Raffaele Di Francia, Angela De Monaco, Mariangela Saggese, Giancarla Iaccarino, Stefania Crisci, Ferdinando Frigeri, Rosaria De Filippi, Massimiliano Berretta, Antonio Pinto
Drugs for targeted therapies are primarily Small Molecules Inhibitors (SMIs), monoclonal antibodies (mAbs), interfering RNA molecules and microRNA. The use of these new agents generates a multifaceted step in the pharmacokinetics (PK) of these drugs. Individual PK variability is often large, and unpredictability observed in the response to the pharmacogenetic profile of the patient (e.g. cytochome P450 enzyme), patient characteristics such as adherence to treatment and environmental factors. Objective This review aims to overview the latest anticancer drugs eligible for targeted therapies and the most recent finding in pharmacogenomics related to toxicity/resistance because either individual gene polymorphisms or acquired mutation in a cancer cell...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28167419/comparative-pharmacokinetic-profiles-of-selected-irreversible-tyrosine-kinase-inhibitors-neratinib-and-pelitinib-with-apigenin-in-rat-plasma-by-uplc-ms-ms
#11
Hadir M Maher, Nourah Z Alzoman, Shereen M Shehata, Ashwag O Abahussain
Neratinib (NER) and pelitinib (PEL) are irreversible tyrosine kinase inhibitors (TKIs) that have been recently employed in cancer treatment. Apigenin (API), among other flavonoids, is known to have antioxidant, anti-proliferative, and carcinogenic effect. API can potentiate the antitumor effect of chemotherapeutic agents and/or alleviate the side effects of many anticancer agents. Since TKIs are mostly metabolized by CYP3A4 enzymes and that API could alter the enzymatic activity, potential drug interactions could be expected following their co-aministration...
April 15, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28025102/somatostatin-receptor-targeted-liposomes-with-diacerein-inhibit-il-6-for-breast-cancer-therapy
#12
Rashmi Bharti, Goutam Dey, Indranil Banerjee, Kaushik Kumar Dey, Sheetal Parida, B N Prashanth Kumar, Chandan Kanta Das, Ipsita Pal, Manabendra Mukherjee, Mridula Misra, Anjan K Pradhan, Luni Emdad, Swadesh K Das, Paul B Fisher, Mahitosh Mandal
Selective targeting to the tumor niche remains a major challenge in successful cancer therapy. Somatostatin receptor 2 (SSTR2) is overexpressed in breast cancer cells thus making this receptor an attractive target for selective guidance of ligand-conjugated drug liposomes to the tumor site. In this study, a synthetic somatostatin analogue (SST) was used as SSTR2 targeting agent and Diacerein was employed as therapeutic molecule. Diacerein loaded liposomes (DNL) were prepared and they were further decorated with the synthetic and stable analogue of somatostatin (SST-DNL)...
March 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27803477/pharmaceutical-investigation-for-individualized-and-optimal-cancer-pharmacotherapy
#13
REVIEW
Tomohiro Terada
 After the year 2000, the treatment of cancer remarkably changed, including the development of outpatient cancer chemotherapy. Meanwhile, we have encountered many clinical problems related to cancer patient pharmacy services. To resolve these problems, I have tried to establish the individualized and optimal cancer pharmacotherapy utilizing the findings of basic research. In this review, three topics of my research will be introduced. 1) In 2005, information regarding the genetic polymorphism of UGT1A1*28 was described in the package insert of the drug irinotecan in the United States...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/27746112/association-of-busulfan-exposure-with-survival-and-toxicity-after-haemopoietic-cell-transplantation-in-children-and-young-adults-a-multicentre-retrospective-cohort-analysis
#14
Imke H Bartelink, Arief Lalmohamed, Elisabeth M L van Reij, Christopher C Dvorak, Rada M Savic, Juliette Zwaveling, Robbert G M Bredius, Antoine C G Egberts, Marc Bierings, Morris Kletzel, Peter J Shaw, Christa E Nath, George Hempel, Marc Ansari, Maja Krajinovic, Yves Théorêt, Michel Duval, Ron J Keizer, Henrique Bittencourt, Moustapha Hassan, Tayfun Güngör, Robert F Wynn, Paul Veys, Geoff D E Cuvelier, Sarah Marktel, Robert Chiesa, Morton J Cowan, Mary A Slatter, Melisa K Stricherz, Cathryn Jennissen, Janel R Long-Boyle, Jaap Jan Boelens
BACKGROUND: Intravenous busulfan combined with therapeutic drug monitoring to guide dosing improves outcomes after allogeneic haemopoietic cell transplantation (HCT). The best method to estimate busulfan exposure and optimum exposure in children or young adults remains unclear. We therefore assessed three approaches to estimate intravenous busulfan exposure (expressed as cumulative area under the curve [AUC]) and associated busulfan AUC with clinical outcomes in children or young adults undergoing allogeneic HCT...
November 2016: Lancet Haematology
https://www.readbyqxmd.com/read/27631462/pediatric-patients-with-solid-or-hematological-tumor-disease-vancomycin-population-pharmacokinetics-and-dosage-optimization
#15
Romain Guilhaumou, Amélie Marsot, Julien Dupouey, Claire Galambrun, Audrey Boulamery, Carole Coze, Nicolas Simon, Nicolas André
BACKGROUND: In pediatric cancer patients, determination of optimal vancomycin dosage is essential because of high risk of inadequate concentrations and bacterial resistance. The aim of this study was to determine vancomycin pharmacokinetic parameters in this population and propose dosage optimization to achieve optimal concentration. METHODS: We retrospectively reviewed the use of vancomycin in pediatric cancer patients with febrile neutropenia (hematological or solid tumor disease)...
October 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27620953/the-pharmacogenomics-of-drug-resistance-to-protein-kinase-inhibitors
#16
Nancy K Gillis, Howard L McLeod
Dysregulation of growth factor cell signaling is a major driver of most human cancers. This has led to development of numerous drugs targeting protein kinases, with demonstrated efficacy in the treatment of a wide spectrum of cancers. Despite their high initial response rates and survival benefits, the majority of patients eventually develop resistance to these targeted therapies. This review article discusses examples of established mechanisms of drug resistance to anticancer therapies, including drug target mutations or gene amplifications, emergence of alternate signaling pathways, and pharmacokinetic variation...
September 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27556889/clinical-pharmacology-drug-drug-interactions-and-safety-of-pazopanib-a-review
#17
REVIEW
Pascaline Boudou-Rouquette, Camille Tlemsani, Benoit Blanchet, Olivier Huillard, Anne Jouinot, Jennifer Arrondeau, Audrey Thomas-Schoemann, Michel Vidal, Jérôme Alexandre, François Goldwasser
In the past decade, treatment options for metastatic renal cell carcinoma and soft-tissue sarcoma have expanded. Pazopanib was discovered during the screening of compounds that suppressed vascular endothelial growth factor receptor-2 (VEGFR-2). As other tyrosine kinase inhibitors (TKI), pazopanib is not totally specific for one target since it also inhibits stem-cell factor receptor (cKIT), platelet-derived growth factor receptors (PDGFRα, β), VEGFR-1 and -3. Areas covered: Clinical pharmacology, drug-drug interactions and safety data published on pazopanib, between January 2006 and April 2016, are reviewed...
December 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27544847/-epigallocatechin-gallate-egcg-nanoethosomes-as-a-transdermal-delivery-system-for-docetaxel-to-treat-implanted-human-melanoma-cell-tumors-in-mice
#18
Bingwu Liao, Hao Ying, Chenhuan Yu, Zhaoyang Fan, Weihua Zhang, John Shi, Huazhong Ying, Nagaiya Ravichandran, Yongquan Xu, Junfeng Yin, Yongwen Jiang, Qizhen Du
(-)-Epigallocatechin-3-O-gallate (EGCG), a versatile natural product in fresh tea leaves and green tea, has been investigated as a preventative treatment for cancers and cardiovascular disease. The objective of this study was to develop EGCG-nanoethosomes for transdermal delivery and to evaluate them for treating subcutaneously implanted human melanoma cell tumors. EGCG-nanoethosomes, composed of 0.2% EGCG, 2% soybean phosphatidylcholine, 30% ethanol, 1% Tween-80 and 0.1% sugar esters, were prepared and characterized using laser transmission electron microscopy...
October 15, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27534647/development-of-a-pharmacokinetic-model-to-describe-the-complex-pharmacokinetics-of-pazopanib-in-cancer-patients
#19
Huixin Yu, Nielka van Erp, Sander Bins, Ron H J Mathijssen, Jan H M Schellens, Jos H Beijnen, Neeltje Steeghs, Alwin D R Huitema
BACKGROUND AND OBJECTIVE: Pazopanib is a multi-targeted anticancer tyrosine kinase inhibitor. This study was conducted to develop a population pharmacokinetic (popPK) model describing the complex pharmacokinetics of pazopanib in cancer patients. METHODS: Pharmacokinetic data were available from 96 patients from three clinical studies. A multi-compartment model including (i) a complex absorption profile, (ii) the potential non-linear dose-concentration relationship and (iii) the potential long-term decrease in exposure was developed...
August 17, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27441411/oncolytic-viruses-in-cancer-treatment-a-review
#20
Sean E Lawler, Maria-Carmela Speranza, Choi-Fong Cho, E Antonio Chiocca
Importance: Oncolytic viruses (OVs) are emerging as important agents in cancer treatment. Oncolytic viruses offer the attractive therapeutic combination of tumor-specific cell lysis together with immune stimulation, therefore acting as potential in situ tumor vaccines. Moreover, OVs can be engineered for optimization of tumor selectivity and enhanced immune stimulation and can be readily combined with other agents. The effectiveness of OVs has been demonstrated in many preclinical studies and recently in humans, with US Food and Drug Administration approval of the oncolytic herpesvirus talimogene laherparepvec in advanced melanoma, a major breakthrough for the field...
June 1, 2017: JAMA Oncology
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