Optimization of bioanalysis of dried blood samples.

INTRODUCTION: Pharmacokinetic/pharmacodynamic modelling has emerged as a valuable technique for understanding drug exposure and response relationships in drug development. Pharmacokinetic data are often obtained by taking multiple blood samples, which may disturb physiological parameters and complicate study designs. Wearable automatic blood sampling systems can improve this limitation by collecting dried blood samples at programmable time points without disrupting cardiovascular parameters. It is the objective of this study to evaluate the bioanalysis of DBS in comparison to conventional blood sampling techniques and to optimize the recovery of various compounds spiked into canine blood dried on filter paper tape. METHODS: Incubated blood samples from Beagle dogs were spiked with 16 different compounds and half of the whole blood sample was centrifuged to obtain plasma. After the dried blood sample drops were dried, liquid chromatography-mass spectrometry methods were used to analyze the samples. The study explored different anticoagulants, sample preparation methods and technical approaches to best determine the compound concentrations in dried blood samples. RESULTS: With the two anticoagulants tested and using the optimized sample preparation methods and technical approaches we employed, the bioanalysis of dried blood samples can provide equivalent results to conventional blood sampling techniques. DISCUSSION: 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 provide a viable alternative to traditional methods of obtaining blood for various other types of studies or analyses.

Thirty years of telemetry-based data acquisition for cardiovascular drug safety evaluation: Applications and optimization.

Conducting safety evaluations of new drugs using conscious animals has been a specialty of our working group for thirty years. In this article, we review the various technical challenges and solutions dealt with over the years to improve both the data quality and the well being of our animal subjects. Of particular interest for us has been the use of telemetry-based data acquisition for conducting studies on cardiovascular (CV) function. This includes the evolving technical aspects of the studies, as well as the development of new applications that take advantage of this technical approach.

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.

INTRODUCTION: A safety pharmacology study detects and evaluates potential side effects of a new drug on physiological function at therapeutic levels and above and, in most cases, prior to the initiation of clinical trials. The aim of this study was to investigate the effects of environmental and biological factors on resting heart rate (HR), a representative cardiac parameter in cardiovascular safety pharmacology. METHODS: Over twenty years, 143 dogs (Beagles, Labradors and mongrels) received implanted telemetry transmitters to measure aortic pressure (AP), left ventricular pressure (LVP), Electrocardiogram (ECG) and body temperature. Throughout the 7-h period of data collection, data were continuously recorded without drug treatment and included the range of HRs resulting from spontaneous physiological changes. Statistics and visualizations were calculated using R and Spotfire. RESULTS: Beagles had a higher HR than the mongrels, while Labradors had a lower HR than mongrels. Labradors were found to have a sex-based difference in HR, with females having a higher HR. A higher HR was observed in young animals of all breeds when they were in contact with humans. The cage system affected the HR of Labradors and mongrels more than Beagles. Larger dogs (e.g. Labrador) have a lower HR than smaller dogs (Beagles). Animals that are younger were found to have more HR variability and have a higher HR than older animals. In addition, older animals reacted less to the application period and human interaction than younger animals. The HR response of animals inside a cage system may depend on the cage system in which they were bred. A familiar cage system typically has less impact on HR. DISCUSSION: 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 used affected, at least in some cases, the HR and its variability. They should therefore be carefully considered when designing safety pharmacology studies to have the highest possible test sensitivity.