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Pharmacokinetic, therapeutic drug monitoring, cancer

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https://www.readbyqxmd.com/read/29749011/rapid-lc-ms-ms-method-for-quantification-of-vinorelbine-and-4-o-deacetylvinorelbine-in-human-whole-blood-suitable-to-monitoring-oral-metronomic-anticancer-therapy
#1
Giuseppe Corona, Milena Gusella, Anna Gaspardo, Gianmaria Miolo, Laura Bertolaso, Elisa Pezzolo, Felice Pasini, Agostino Steffan, Donatella Caruso
A rapid and sensitive LC-MS/MS method for therapeutic drug monitoring oral vinorelbine (VRL) metronomic anticancer chemotherapy has been developed and validated. Analysis of VRL and its main active metabolite 4-O-deacetylvinorelbine (M1) was performed in whole blood matrix. Both analytes were extracted by protein precipitation and separated on an Onyx monolith C18, 50 x 2 mm column then quantified by positive electrospray ionization and multiple reaction monitoring mode. The LLOQ was 0.05 ng/mL for both VRL and M1...
May 10, 2018: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29721074/polyamine-targeting-gefitinib-prodrug-and-its-near-infrared-fluorescent-theranostic-derivative-for-monitoring-drug-delivery-and-lung-cancer-therapy
#2
Xinyu Song, Xiaoyue Han, Fabiao Yu, Xiaoyu Zhang, Lingxin Chen, Changjun Lv
The therapy of non-small-cell lung cancer (NSCLC) is challenging because of poor prognosis. There are urgent demands for targeting anti-tumor drugs with reliable efficacy and clear pharmacokinetics. Methods : We designed and synthesized an active tumor-targeting prodrug for the precision therapy of NSCLC. The prodrug polyamine analog Gefitinib (PPG) was derived from the conjugation between a tumor-targeting ligand polyamine analog (PA) and an epidermal growth factor receptor tyrosine kinase inhibitor Gefitinib via a cleavable disulfide linker...
2018: Theranostics
https://www.readbyqxmd.com/read/29477930/acquired-resistance-to-egfr-targeted-therapy-in-non-small-cell-lung-cancer-mechanisms-and-therapeutic-strategies
#3
REVIEW
Sun Min Lim, Nicholas L Syn, Byoung Chul Cho, Ross A Soo
The tyrosine kinase inhibitors (TKIs) directed at sensitizing mutations in the epidermal growth factor receptor (EGFR) gene represents a critical pillar in non-small cell lung cancer treatment. Despite the excellent disease control with initial EGFR TKI therapy, acquired resistance is ubiquitous and remains a key challenge. Investigations into the mechanisms which foster resistance to EGFR TKIs has led to the discovery of novel biomarkers and drug targets, and in turn has enabled the development of third-generation TKIs and proposals for rational therapeutic combinations...
April 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29474420/a-new-high-performance-liquid-chromatography-tandem-mass-spectrometry-method-for-the-determination-of-paclitaxel-and-6%C3%AE-hydroxy-paclitaxel-in-human-plasma-development-validation-and-application-in-a-clinical-pharmacokinetic-study
#4
Bianca Posocco, Mauro Buzzo, Andrea Follegot, Luciana Giodini, Roberto Sorio, Elena Marangon, Giuseppe Toffoli
Paclitaxel belongs to the taxanes family and it is used, alone or in multidrug regimens, for the therapy of several solid tumours, such as breast-, lung-, head and neck-, and ovarian cancer. Standard dosing of chemotherapy does not take into account the many inter-patient differences that make drug exposure highly variable, thus leading to the insurgence of severe toxicity. This is particularly true for paclitaxel considering that a relationship between haematological toxicity and plasma exposure was found...
2018: PloS One
https://www.readbyqxmd.com/read/29453635/monitoring-of-erlotinib-in-pancreatic-cancer-patients-during-long-time-administration-and-comparison-to-a-physiologically-based-pharmacokinetic-model
#5
Andrea Gruber, Martin Czejka, Philipp Buchner, Marie Kitzmueller, Nairi Kirchbaumer Baroian, Christian Dittrich, Azra Sahmanovic Hrgovcic
PURPOSE: In this study, a therapeutic drug monitoring (TDM) of erlotinib in pancreatic cancer patients was performed over 50 weeks to reveal possible alterations in erlotinib plasma concentrations. Additionally, a physiologically based pharmacokinetic (PBPK) model was created to assess such variations in silico. METHODS: Patients with advanced pancreatic cancer received a chemotherapeutic combination of 100 mg erlotinib q.d., 500-900 mg capecitabine b.d. and 5 mg/kg bevacizumab q...
April 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29345521/development-and-validation-of-an-elisa-to-study-panitumumab-pharmacokinetics
#6
Céline Desvignes, Christophe Passot, David Ternant, Morgane Caulet, Caroline Guérineau, Thierry Lecomte, Gilles Paintaud
AIM: Panitumumab is a monoclonal antibody directed against EGFR that is approved for the treatment of metastatic colorectal cancer. To investigate its pharmacokinetics and concentration-response relationship, a validated assay is required. RESULTS: An ELISA assay was developed and validated according to international recommendations. Six calibrators (ranging from 0.1 to 20 mg/l) plus one anchor point (50 mg/l) and three quality controls (0.45, 2 and 8 mg/l) were defined...
January 18, 2018: Bioanalysis
https://www.readbyqxmd.com/read/29317432/-in-silico-evaluation-of-pharmacokinetic-optimization-for-antimitogram-based-clinical-trials
#7
Skerdi Haviari, Benoît You, Michel Tod
Antimitograms are prototype in vitro tests for evaluating chemotherapeutic efficacy using patient-derived primary cancer cells. These tests might help optimize treatment from a pharmacodynamic standpoint by guiding treatment selection. However, they are technically challenging and require refinements and trials to demonstrate benefit to be widely used. In this study, we performed simulations aimed at exploring how to validate antimitograms and how to complement them by pharmacokinetic optimization. A generic model of advanced cancer, including pharmacokinetic-pharmacodynamic monitoring, was used to link dosing schedules with progression-free survival (PFS), as built from previously validated modules...
April 1, 2018: Cancer Research
https://www.readbyqxmd.com/read/29096853/plasma-filtration-for-the-controlled-removal-of-liposomal-therapeutics-from-the-apheretic-site-of-view
#8
M Blaha, J Martinkova, M Lanska, S Filip, J Malakova, O Kubecek, J Bezouska, J Spacek
INTRODUCTION: Nanoparticle-based drug delivery systems can overcome the dose-limited toxicity of cytostatics. Pegylated doxorubicin-containing liposomes (PLD) are able to reduce cardiotoxicity. PLD quickly (in 2 days) attains therapeutic concentration in tumorous tissue (kinetic targeting), while its distribution in normal tissue, which is a cause of mucocutaneous toxicity (MCT), is delayed. We examined PLD extracorporeal removal effectivity, using plasma filtration (PF) to determine whether the drug could be withheld prior to its organ distribution responsible for MCT toxicity...
November 2017: Atherosclerosis. Supplements
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/28916378/clinical-pharmacology-of-anti-angiogenic-drugs-in-oncology
#10
REVIEW
P Gougis, J Wassermann, J P Spano, N Keynan, C Funck-Brentano, J E Salem
Abnormal vasculature proliferation is one of the so-called hallmarks of cancer. Angiogenesis inhibitor therapies are one of the major breakthroughs in cancer treatment in the last two decades. Two types of anti-angiogenics have been approved: monoclonal antibodies and derivatives, which are injected and target the extracellular part of a receptor, and protein kinase inhibitors, which are orally taken small molecules targeting the intra-cellular Adenosine Triphosphate -pocket of different kinases. They have become an important part of some tumors' treatment, both in monotherapy or in combination...
September 1, 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28906558/effects-of-rolapitant-administered-intravenously-or-orally-on-the-pharmacokinetics-of-digoxin-p-glycoprotein-substrate-and-sulfasalazine-breast-cancer-resistance-protein-substrate-in-healthy-volunteers
#11
Xiaodong Wang, Zhi-Yi Zhang, Sujata Arora, Lorraine Hughes, Jing Wang, Daniel Powers, Jennifer Christensen, Sharon Lu, Vikram Kansra
Rolapitant is a selective and long-acting neurokinin-1 receptor antagonist approved in an oral formulation in combination with other antiemetic agents for the prevention of delayed chemotherapy-induced nausea and vomiting in adults. Four open-label phase 1 studies evaluated the safety and drug-drug interactions of a single dose of rolapitant given intravenously (166.5 mg) or orally (180 mg) with oral digoxin (0.5 mg) or sulfasalazine (500 mg), probe substrates for the P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), respectively...
February 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28641556/pharmacogenetic-and-pharmacokinetic-dose-individualization-of-the-taxane-chemotherapeutic-drugs-paclitaxel-and-docetaxel
#12
REVIEW
Natalia B Andriguetti, Suziane Raymundo, Marina V Antunes, Magda S Perassolo, Simone G Verza, Edna S Suyenaga, Rafael Linden
BACKGROUND: The taxane drugs paclitaxel and docetaxel, widely used on cancer chemotherapy, are currently dosed mainly based on body-surface area. This approach is associated with wide interindividual variability in drug exposure, leading to suboptimal dosing for many patients. METHODS: The available evidence supporting dose individualization strategies for paclitaxel and docetaxel were reviewed, focusing mainly on the application of therapeutic drug monitoring by a priori pharmacogenetic data or a posteriori drug measurements in biological fluids...
2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28634655/effect-of-adherence-on-pharmacokinetic-pharmacodynamic-relationships-of-oral-targeted-anticancer-drugs
#13
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...
January 2018: 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
#14
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
#15
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
#16
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...
February 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28516432/measurement-of-piperacillin-plasma-concentrations-in-cancer-patients-with-suspected-infection
#17
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...
October 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-via-analysis-of-343-courses
#18
Frank P Tverdek, Sang Taek Heo, Samuel L Aitken, Bruno Granwehr, Dimitrios P Kontoyiannis
Posaconazole is the preferred mold-active azole for prophylaxis against invasive fungal infections (IFIs) in patients with hematological malignancy. 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 for patients with hematological malignancy. A retrospective cohort of all consecutive adult inpatients with hematological malignancy who received ≥3 days of tablet or intravenous posaconazole therapy for primary IFI prophylaxis at the M...
August 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-receiving-erlotinib-treatment
#19
Zinnia P Parra-Guillen, Peter B Berger, Manuel Haschke, Massimiliano Donzelli, Daria Winogradova, Bogumila Pfister, Martin Früh, Silke Gillessen, Stephan Krähenbühl, Charlotte Kloft, 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 two oral probe drugs midazolam (2 mg) and caffeine (100 mg) 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...
October 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
#20
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
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