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Predicting QRS and PR interval prolongations in humans using nonclinical data
Risk of cardiac conduction slowing (QRS/PR prolongations) is assessed prior to clinical trials using in vitro and in vivo studies. Understanding the quantitative translation of these studies to theExpand
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PKPD modelling of PR and QRS intervals in conscious dogs using standard safety pharmacology data.
INTRODUCTION Pharmacokinetic-pharmacodynamic (PKPD) modelling can improve safety assessment, but few PKPD models describing drug-induced QRS and PR prolongations have been published. ThisExpand
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Quantifying Drug‐Induced Bone Marrow Toxicity Using a Novel Haematopoiesis Systems Pharmacology Model
Haematological toxicity associated with cancer therapeutics is monitored by changes in blood cell count, and their primary effect is on proliferative progenitors in the bone marrow. UsingExpand
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Understanding Hematological Toxicities Using Mathematical Modeling
Balancing antitumor efficacy with toxicity is a significant challenge, and drug‐induced myelosuppression is a common dose‐limiting toxicity of cancer treatments. Mathematical modeling has proven toExpand
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A tutorial on model informed approaches to cardiovascular safety with focus on cardiac repolarisation
Drugs can affect the cardiovascular (CV) system either as an intended treatment or as an unwanted side effect. In both cases, drug-induced cardiotoxicities such as arrhythmia and unfavourableExpand
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Discovery and pharmacological characterization of AZD3229, a potent KIT/PDGFRα inhibitor for treatment of gastrointestinal stromal tumors
AZD3229 demonstrates pan-KIT/PDGFRα activity in several preclinical models and is a promising agent for the treatment of GIST. Getting the GIST of treatment Gastrointestinal stromal tumor, or GIST,Expand
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Current and future approaches to nonclinical cardiovascular safety assessment.
Our goal is to accurately predict all types of cardiovascular events in patients utilising nonclinical cardiovascular safety data. In the past two decades, cardiovascular safety science has primarilyExpand
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Semi‐mechanistic modelling platform to assess cardiac contractility and haemodynamics in preclinical cardiovascular safety profiling of new molecular entities
Cardiovascular safety is one of the most frequent causes of safety‐related attrition both preclinically and clinically. Preclinical cardiovascular safety is routinely assessed using dog telemetryExpand
Importance of Stability Analysis When Using Nonlinear Semimechanistic Models to Describe Drug‐Induced Hematotoxicity
TLDR
We study the parametric dependence of stable and unstable solutions of several Friberg‐type models and highlight the risks associated with system instability in the context of nonlinear mixed effects modeling. Expand