Brian D. Guth
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View article: Optimization of bioanalysis of dried blood samples
Optimization of bioanalysis of dried blood samples Open
Automated blood sampling systems have the potential to provide increased numbers of blood samples, providing substantially more Pharmacokinetic data within safety pharmacology studies without disrupting physiological parameters. They can p…
View article: The impact of environmental and biological factors on the resting heart rate of dogs as assessed using 20 years of data from safety pharmacology studies
The impact of environmental and biological factors on the resting heart rate of dogs as assessed using 20 years of data from safety pharmacology studies Open
This retrospective data base evaluation has demonstrated the impact of environmental and biological factors on cardiovascular parameters in the context of performing safety pharmacology studies. Breed, sex, age and the type of cage system …
View article: Time for a Fully Integrated Nonclinical–Clinical Risk Assessment to Streamline QT Prolongation Liability Determinations: A Pharma Industry Perspective
Time for a Fully Integrated Nonclinical–Clinical Risk Assessment to Streamline QT Prolongation Liability Determinations: A Pharma Industry Perspective Open
Defining an appropriate and efficient assessment of drug‐induced corrected QT interval (QTc) prolongation (a surrogate marker of torsades de pointes arrhythmia) remains a concern of drug developers and regulators worldwide. In use for over…
View article: Echocardiographic and hemodynamic indices of myocardial contractility simultaneously evaluated in telemetered beagle dogs: A HESI-sponsored cross-company evaluation
Echocardiographic and hemodynamic indices of myocardial contractility simultaneously evaluated in telemetered beagle dogs: A HESI-sponsored cross-company evaluation Open
Comparing data from telemetry-only groups to those that included echocardiography collections showed no effect in the ability to interpret test article-related effects, providing the foundation for the inclusion of echocardiography without…
View article: Comparison of in vitro and computational experiments on the relation of inter-beat interval and duration of repolarization in a specific type of human induced pluripotent stem cell-derived cardiomyocytes
Comparison of in vitro and computational experiments on the relation of inter-beat interval and duration of repolarization in a specific type of human induced pluripotent stem cell-derived cardiomyocytes Open
We compared a published computational model of the action potential of a specific type of human induced pluripotent stem cell -derived cardiomyocytes (hiPSC-CM) with experimental field potential data with regard to their inter-beat interva…
View article: Considerations for an In Vitro, Cell-Based Testing Platform for Detection of Drug-Induced Inotropic Effects in Early Drug Development. Part 2: Designing and Fabricating Microsystems for Assaying Cardiac Contractility With Physiological Relevance Using Human iPSC-Cardiomyocytes
Considerations for an In Vitro, Cell-Based Testing Platform for Detection of Drug-Induced Inotropic Effects in Early Drug Development. Part 2: Designing and Fabricating Microsystems for Assaying Cardiac Contractility With Physiological Relevance Using Human iPSC-Cardiomyocytes Open
Contractility of the myocardium engines the pumping function of the heart and is enabled by the collective contractile activity of its muscle cells: cardiomyocytes. The effects of drugs on the contractility of human cardiomyocytes in vitro…
View article: Considerations for an In Vitro, Cell-Based Testing Platform for Detection of Adverse Drug-Induced Inotropic Effects in Early Drug Development. Part 1: General Considerations for Development of Novel Testing Platforms
Considerations for an In Vitro, Cell-Based Testing Platform for Detection of Adverse Drug-Induced Inotropic Effects in Early Drug Development. Part 1: General Considerations for Development of Novel Testing Platforms Open
Drug-induced effects on cardiac contractility can be assessed through the measurement of the maximal rate of pressure increase in the left ventricle (LVdP/dtmax) in conscious animals, and such studies are often conducted at the late stage …
View article: Drug safety Africa: An overview of safety pharmacology & toxicology in South Africa
Drug safety Africa: An overview of safety pharmacology & toxicology in South Africa Open
This meeting report is based on presentations given at the first Drug Safety Africa Meeting in Potchefstroom, South Africa from November 20-22, 2018 at the North-West University campus. There were 134 attendees (including 26 speakers and 3…
View article: The evaluation of endpoint variability and implications for study statistical power and sample size in conscious instrumented dogs
The evaluation of endpoint variability and implications for study statistical power and sample size in conscious instrumented dogs Open
We describe a statistical procedure to quantitatively evaluate the acute cardiac effects from studies conducted across six sites and objectively examine the variability and sensitivity that were difficult or impossible to calculate consist…
View article: Repeated anaesthesia with isoflurane and medetomidine-midazolam-fentanyl in guinea pigs and its influence on physiological parameters
Repeated anaesthesia with isoflurane and medetomidine-midazolam-fentanyl in guinea pigs and its influence on physiological parameters Open
Repeated anaesthesia may be required in experimental protocols and in daily veterinary practice, but anaesthesia is known to alter physiological parameters in GPs (Cavia porcellus, GPs). This study investigated the effects of repeated anae…
View article: GLP in safety pharmacology studies: Report card after 15 years
GLP in safety pharmacology studies: Report card after 15 years Open
The pivotal role of safety pharmacology in the safety testing of new drugs is now well established, having received a large impetus through the regulatory requirement of this type of study and the appearance of the ICHS7A guidance in 2001 …
View article: An evaluation of the utility of LVdP/dt40, QA interval, LVdP/dtmin and Tau as indicators of drug-induced changes in contractility and lusitropy in dogs
An evaluation of the utility of LVdP/dt40, QA interval, LVdP/dtmin and Tau as indicators of drug-induced changes in contractility and lusitropy in dogs Open
These findings indicate that this experimental model can accurately and consistently detect changes in cardiac contractility, across multiple sites and instrumentation systems. While LVdP/dt40 produced responses similar to LVdP/dtmax, the …
View article: Comparison of Physiological Parameters and Anaesthesia Specific Observations during Isoflurane, Ketamine-Xylazine or Medetomidine-Midazolam-Fentanyl Anaesthesia in Male Guinea Pigs
Comparison of Physiological Parameters and Anaesthesia Specific Observations during Isoflurane, Ketamine-Xylazine or Medetomidine-Midazolam-Fentanyl Anaesthesia in Male Guinea Pigs Open
Guinea pigs (GPs) are difficult to anaesthetize successfully, the choices for anaesthesia are limited and physiological parameters are likely to be influenced substantially under anaesthesia. We implanted blood pressure radio-telemetry dev…
View article: Cardiovascular safety pharmacology studies in dogs enabled for a poorly soluble molecule using spray-dried dispersion: Impact on lead selection
Cardiovascular safety pharmacology studies in dogs enabled for a poorly soluble molecule using spray-dried dispersion: Impact on lead selection Open
The aim of this study was to identify an adequate formulation for a poorly soluble lead molecule (BI-A) that would achieve sufficiently high plasma concentrations after oral administration in dogs to enable a robust cardiovascular safety p…
View article: Successful implantation of an abdominal aortic blood pressure transducer and radio-telemetry transmitter in guinea pigs — Anaesthesia, analgesic management and surgical methods, and their influence on hemodynamic parameters and body temperature
Successful implantation of an abdominal aortic blood pressure transducer and radio-telemetry transmitter in guinea pigs — Anaesthesia, analgesic management and surgical methods, and their influence on hemodynamic parameters and body temperature Open
A high survival rate in telemetered GPs is possible. We achieved this through a procedure with minimal stress through habituation and planning, continuous warming during anaesthesia, an optimal anaesthetic and analgesic management, efficie…