keyword
MENU ▼
Read by QxMD icon Read
search

Pharmacometrics

keyword
https://www.readbyqxmd.com/read/29156443/ensuring-quality-pharmacokinetic-analyses-in-antimicrobial-drug-development-programs
#1
REVIEW
Elizabeth A Lakota, Justin C Bader, Christopher M Rubino
Pharmacokinetic studies and analyses can be expensive, time consuming, and labor intensive. However, it is crucial to understand that much of what happens in antimicrobial drug development, such as dose-selection and clinical study design, can be optimized with a strong understanding of the underlying pharmacokinetics of an agent. In this way, pharmacokinetics forms the bedrock of a pharmacometric approach to antimicrobial development. Thus, pharmacokinetic analyses must be considered an integral part of a drug's development strategy and studies must be planned and designed accordingly...
November 17, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29136155/a-model-informed-preclinical-approach-for-prediction-of-clinical-pharmacodynamic-interactions-of-anti-tb-drug-combinations
#2
Oskar Clewe, Sebastian G Wicha, Corné P de Vogel, Jurriaan E M de Steenwinkel, Ulrika S H Simonsson
Background: Identification of pharmacodynamic interactions is not reasonable to carry out in a clinical setting for many reasons. The aim of this work was to develop a model-informed preclinical approach for prediction of clinical pharmacodynamic drug interactions in order to inform early anti-TB drug development. Methods: In vitro time-kill experiments were performed with Mycobacterium tuberculosis using rifampicin, isoniazid or ethambutol alone as well as in different combinations at clinically relevant concentrations...
November 9, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29103208/model-selection-and-averaging-of-nonlinear-mixed-effect-models-for-robust-phase-iii-dose-selection
#3
Yasunori Aoki, Daniel Röshammar, Bengt Hamrén, Andrew C Hooker
Population model-based (pharmacometric) approaches are widely used for the analyses of phase IIb clinical trial data to increase the accuracy of the dose selection for phase III clinical trials. On the other hand, if the analysis is based on one selected model, model selection bias can potentially spoil the accuracy of the dose selection process. In this paper, four methods that assume a number of pre-defined model structure candidates, for example a set of dose-response shape functions, and then combine or select those candidate models are introduced...
November 4, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28972401/mathematical-modeling-of-efficacy-and-safety-for-anticancer-drugs-clinical-development
#4
Silvia Maria Lavezzi, Elisa Borella, Letizia Carrara, Giuseppe De Nicolao, Paolo Magni, Italo Poggesi
Drug attrition in oncology clinical development is higher than other therapeutic areas. In this context, pharmacometric modeling represents a useful tool to explore drug efficacy in earlier phases of clinical development, anticipating overall survival using quantitative model-based metrics. Furthermore, modeling approaches can be used to characterize earlier the safety and tolerability profile of drug candidates, and, thus, the risk-benefit ratio and the therapeutic index, supporting the design of optimal treatment regimens and accelerating the whole process of clinical drug development...
October 3, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28948582/abstracts-for-american-conference-on-pharmacometrics-2017-acop8
#5
(no author information available yet)
No abstract text is available yet for this article.
October 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28948580/the-american-conference-on-pharmacometrics-2017-acop8
#6
Brenda Cirincione, Navin Goyal, Rene Bruno
No abstract text is available yet for this article.
October 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28925019/inclusion-of-pregnant-and-breastfeeding-women-in-research-efforts-and-initiatives
#7
Sílvia M Illamola, Christina Bucci-Rechtweg, Maged M Costantine, Ekaterini Tsilou, Catherine M Sherwin, Anne Zajicek
Pregnant and breastfeeding women have been rendered therapeutic orphans as they have been historically excluded from clinical trials. Labelling for most approved drugs does not provide information about safety and efficacy during pregnancy. This lack of data is mainly due to ethico-legal challenges that have remained entrenched in the post-diethylstilbestrol and thalidomide era, and that have led to pregnancy being viewed in the clinical trial setting primarily through a pharmacovigilance lens. Policy considerations that encourage and/or require the inclusion of pregnant or lactating women in clinical trials may address the current lack of available information...
September 19, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921644/clinical-pharmacology-considerations-for-the-development-of-immune-checkpoint-inhibitors
#8
Jennifer Sheng, Shivani Srivastava, Kinjal Sanghavi, Zheng Lu, Brian J Schmidt, Akintunde Bello, Manish Gupta
Immuno-oncology works through activation of the patient's immune system against cancer, with several advantages over other treatment approaches, including cytotoxic agents and molecular-targeted therapies. The most notable feature of immuno-oncology treatments is the nature of the patient responses achieved, which can be more durable and sustained than with other modalities. Increased understanding of immune system complexity has provided a number of opportunities to advance several strategies for the development of immuno-oncology therapies...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921642/clinical-pharmacology-tools-and-evaluations-to-facilitate-comprehensive-dose-finding-in-oncology-a-continuous-risk-benefit-approach
#9
Julie M Bullock, Tiffany Lin, Sanela Bilic
Targeted therapies are now considered an integral component in the treatment armamentarium for many malignancies, and the approach to developing these drugs needs to be refined from the previous cytotoxic paradigm of toxicity-guided dose finding and identification of maximum tolerated dose to a paradigm driven by target activity. Moving away from the toxicity-driven dose finding and justification model requires an integrated approach in order to adequately characterize the risk-benefit of a drug. This approach starts with understanding the importance of collecting samples for pharmacokinetic and pharmacodynamic assessments in all phases of clinical development to fully characterize the pharmacokinetics and identify covariates and then correlating exposure to key markers of safety and efficacy in pharmacometric analyses to perform a robust risk-benefit assessment and establish the right dose...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28918570/mathematical-description-of-drug-target-interactions-application-to-biologics-that-bind-to-targets-with-two-binding-sites
#10
Leonid Gibiansky, Ekaterina Gibiansky
The emerging discipline of mathematical pharmacology occupies the space between advanced pharmacometrics and systems biology. A characteristic feature of the approach is application of advance mathematical methods to study the behavior of biological systems as described by mathematical (most often differential) equations. One of the early application of mathematical pharmacology (that was not called this name at the time) was formulation and investigation of the target-mediated drug disposition (TMDD) model and its approximations...
September 16, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28881097/notice-of-temporary-withdrawal
#11
(no author information available yet)
No abstract text is available yet for this article.
September 7, 2017: Pediatric Pulmonology
https://www.readbyqxmd.com/read/28861695/pharmacometrics-models-with-hidden-markovian-dynamics
#12
Marc Lavielle
The aim of this paper is to provide an overview of pharmacometric models that involve some latent process with Markovian dynamics. Such models include hidden Markov models which may be useful for describing the dynamics of a disease state that jumps from one state to another at discrete times. On the contrary, diffusion models are continuous-time and continuous-state Markov models that are relevant for modelling non observed phenomena that fluctuate continuously and randomly over time. We show that an extension of these models to mixed effects models is straightforward in a population context...
August 31, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28735000/application-of-pharmacometrics-and-quantitative-systems-pharmacology-to-cancer-therapy-the-example-of-luminal-a-breast-cancer
#13
REVIEW
Brett Fleisher, Ashley N Brown, Sihem Ait-Oudhia
Breast cancer (BC) is the most common cancer in women, and the second most frequent cause of cancer-related deaths in women worldwide. It is a heterogeneous disease composed of multiple subtypes with distinct morphologies and clinical implications. Quantitative systems pharmacology (QSP) is an emerging discipline bridging systems biology with pharmacokinetics (PK) and pharmacodynamics (PD) leveraging the systematic understanding of drugs' efficacy and toxicity. Despite numerous challenges in applying computational methodologies for QSP and mechanism-based PK/PD models to biological, physiological, and pharmacological data, bridging these disciplines has the potential to enhance our understanding of complex disease systems such as BC...
July 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28722322/advanced-methods-for-dose-and-regimen-finding-during-drug-development-summary-of-the-ema-efpia-workshop-on-dose-finding-london-4-5-december-2014
#14
F T Musuamba, E Manolis, N Holford, Sya Cheung, L E Friberg, K Ogungbenro, M Posch, Jwt Yates, S Berry, N Thomas, S Corriol-Rohou, B Bornkamp, F Bretz, A C Hooker, P H Van der Graaf, J F Standing, J Hay, S Cole, V Gigante, K Karlsson, T Dumortier, N Benda, F Serone, S Das, A Brochot, F Ehmann, R Hemmings, I Skottheim Rusten
Inadequate dose selection for confirmatory trials is currently still one of the most challenging issues in drug development, as illustrated by high rates of late-stage attritions in clinical development and postmarketing commitments required by regulatory institutions. In an effort to shift the current paradigm in dose and regimen selection and highlight the availability and usefulness of well-established and regulatory-acceptable methods, the European Medicines Agency (EMA) in collaboration with the European Federation of Pharmaceutical Industries Association (EFPIA) hosted a multistakeholder workshop on dose finding (London 4-5 December 2014)...
July 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28711678/linezolid-in-liver-failure-exploring-the-value-of-the-maximal-liver-function-capacity-limax-test-in-a-pharmacokinetic-pilot-study
#15
Sebastian G Wicha, Otto R Frey, Anka C Roehr, Johann Pratschke, Martin Stockmann, Rawan Alraish, Tilo Wuensch, Magnus Kaffarnik
Patients in the intensive care unit frequently require antibiotic treatment. Liver impairment poses substantial challenges for dose selection in these patients. The aim of the present pilot study was to assess the novel maximal liver function capacity (LiMAx test) in comparison with conventional liver function markers as covariates of drug clearance in liver failure using linezolid as a model drug. A total of 28 patients with different degrees of liver failure were recruited. LiMAx test as well as plasma, dialysate and urine sampling were performed under linezolid steady-state therapy (600 mg twice daily)...
October 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28688237/antibacterial-drug-development-program-successes-and-failures-a-pharmacometric-explanation
#16
REVIEW
Paul G Ambrose
My thesis is a simple one. We have not been doing a good enough job selecting dose regimens for serious infections during the drug development process. If we are to do a better job in the future, we need to revisit some uncomfortable places. That is, some notable program failures. To be clear, we are not revisiting program failures to make anyone uncomfortable or cast aspersions - but rather so that we sow the seeds for a better future. To that end, we will examine program failures and successes through a pharmacometric lens...
July 5, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28684136/open-innovation-towards-sharing-of-data-models-and-workflows
#17
REVIEW
Daniela J Conrado, Mats O Karlsson, Klaus Romero, Céline Sarr, Justin J Wilkins
Sharing of resources across organisations to support open innovation is an old idea, but which is being taken up by the scientific community at increasing speed, concerning public sharing in particular. The ability to address new questions or provide more precise answers to old questions through merged information is among the attractive features of sharing. Increased efficiency through reuse, and increased reliability of scientific findings through enhanced transparency, are expected outcomes from sharing...
November 15, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28662542/quantitative-disease-progression-model-of-%C3%AE-1-proteinase-inhibitor-therapy-on-computed-tomography-lung-density-in-patients-with-%C3%AE-1-antitrypsin-deficiency
#18
Michael A Tortorici, James A Rogers, Oliver Vit, Martin Bexon, Robert A Sandhaus, Jonathan Burdon, Joanna Chorostowska-Wynimko, Philip Thompson, James Stocks, Noel G McElvaney, Kenneth R Chapman, Jonathan M Edelman
AIMS: Early-onset emphysema attributed to α-1 antitrypsin deficiency (AATD) is frequently overlooked and undertreated. RAPID-RCT/RAPID-OLE, the largest clinical trials of purified human α-1 proteinase inhibitor (A1 -PI; 60 mg kg(-1)  week(-1) ) therapy completed to date, demonstrated for the first time that A1 -PI is clinically effective in slowing lung tissue loss in AATD. A posthoc pharmacometric analysis was undertaken to further explore dose, exposure and response. METHODS: A disease progression model was constructed, utilizing observed A1 -PI exposure and lung density decline rates (measured by computed tomography) from RAPID-RCT/RAPID-OLE, to predict effects of population variability and higher doses on A1 -PI exposure and clinical response...
November 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28657202/assessing-pharmacodynamic-interactions-in-mice-using-the-multistate-tuberculosis-pharmacometric-and-general-pharmacodynamic-interaction-models
#19
Chunli Chen, Sebastian G Wicha, Gerjo J de Knegt, Fatima Ortega, Laura Alameda, Veronica Sousa, Jurriaan E M de Steenwinkel, Ulrika S H Simonsson
The aim of this study was to investigate pharmacodynamic interactions in mice infected with Mycobacterium tuberculosis using population pharmacokinetics, the Multistate Tuberculosis Pharmacometric (MTP) model, and the General Pharmacodynamic Interaction (GPDI) model. Rifampicin, isoniazid, ethambutol or pyrazinamide were administered in monotherapy for 4 weeks. Rifampicin and isoniazid showed effects in monotherapy, whereas the animals became moribund after 7 days with ethambutol or pyrazinamide alone. No pharmacodynamic interactions were observed against fast-multiplying bacteria...
June 28, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28634883/a-minimal-continuous-time-markov-pharmacometric-model
#20
Emilie Schindler, Mats O Karlsson
In this work, an alternative model to discrete-time Markov model (DTMM) or standard continuous-time Markov model (CTMM) for analyzing ordered categorical data with Markov properties is presented: the minimal CTMM (mCTMM). Through a CTMM reparameterization and under the assumption that the transition rate between two consecutive states is independent on the state, the Markov property is expressed through a single parameter, the mean equilibration time, and the steady-state probabilities are described by a proportional odds (PO) model...
June 20, 2017: AAPS Journal
keyword
keyword
5395
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"