Contribution of preclinical MRI to responsible animal research: living up to the 3R principle

Wachsmuth, Lydia; Mensen, Armand; Barca, Cristina; Wiart, Marlène; Tristão‐Pereira, Catarina; Busato, Alice; Waiczies, Sonia; Himmelreich, Uwe; Millward, Jason M.; Reimann, Henning Matthias; Jelescu, Ileana O.; Marzola, Pasquina; Pradier, Bruno; Viola, Angèle; Faber, Cornelius

doi:10.1007/s10334-021-00929-w

Cited by 11 publications

(11 citation statements)

References 18 publications

(14 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, experimentally measuring drug exposure in target tissues remains difficult and presents ethical concerns. Since William Russel and Rex Burch proposed the 3Rs principle, namely replacement, reduction, and refinement for animal welfare in 1959, more and more studies have focused on the improvement of animal experimental protocols, which has also brought challenges to traditional PK studies [ 27 , 28 ]. In recent decades, computational technologies have rapidly developed and been increasingly applied in preclinical phases [ 29 , 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of Novel Furoxan/Coumarin Hybrids in Rats Using LC-MS/MS Method and Physiologically Based Pharmacokinetic Model

Yuan

Wang

et al. 2023

Molecules

View full text Add to dashboard Cite

Novel furoxan/coumarin hybrids were synthesized, and pharmacologic studies showed that the compounds displayed potent antiproliferation activities via downregulating both the phosphatidylinositide 3-kinase (PI3K) pathway and the mitogen-activated protein kinase (MAPK) pathway. To investigate the preclinical pharmacokinetic (PK) properties of three candidate compounds (CY-14S-4A83, CY-16S-4A43, and CY-16S-4A93), liquid chromatography, in tandem with the mass spectrometry LC-MS/MS method, was developed and validated for the simultaneous determination of these compounds. The absorption, distribution, metabolism, and excretion (ADME) properties were investigated in in vitro studies and in rats. Meanwhile, physiologically based pharmacokinetic (PBPK) models were constructed using only in vitro data to obtain detailed PK information. Good linearity was observed over the concentration range of 0.01–1.0 μg/mL. The free drug fraction (fu) values of the compounds were less than 3%, and the clearance (CL) values were 414.5 ± 145.7 mL/h/kg, 2624.6 ± 648.4 mL/h/kg, and 500.6 ± 195.2 mL/h/kg, respectively. The predicted peak plasma concentration (Cmax) and the area under the concentration-time curve (AUC) were overestimated for the CY-16S-4A43 PBPK model compared with the experimental ones (fold error > 2), suggesting that tissue accumulation and additional elimination pathways may exist. In conclusion, the LC-MS/MS method was successively applied in the preclinical PK studies, and the detailed information from PBPK modeling may improve decision-making in subsequent new drug development.

show abstract

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of Novel Furoxan/Coumarin Hybrids in Rats Using LC-MS/MS Method and Physiologically Based Pharmacokinetic Model

Yuan

Wang

et al. 2023

Molecules

View full text Add to dashboard Cite

show abstract

“…According to the latest European Union (EU) statistics, a large number of animals (10.4 million in 2019 alone in the EU) are used for medical research. With the rapid advent of preclinical imaging [ 4 ], many of these would be part of research projects making use of preclinical imaging techniques, which in turn has a proven reduction effect on animal numbers due to repetitive imaging and less need of multiple subgroups to cover a disease development timeline [ 9 ]. Importantly, the ethical rule of the 3Rs (reduction, refinement and replacement) exists since 1959 [ 10 ] and all reputable funding bodies and scientific journals require adherence to said ethical principles.…”

Section: Introductionmentioning

confidence: 99%

Community Survey Results Show that Standardisation of Preclinical Imaging Techniques Remains a Challenge

et al. 2022

View full text Add to dashboard Cite

Purpose To support acquisition of accurate, reproducible and high-quality preclinical imaging data, various standardisation resources have been developed over the years. However, it is unclear the impact of those efforts in current preclinical imaging practices. To better understand the status quo in the field of preclinical imaging standardisation, the STANDARD group of the European Society of Molecular Imaging (ESMI) put together a community survey and a forum for discussion at the European Molecular Imaging Meeting (EMIM) 2022. This paper reports on the results from the STANDARD survey and the forum discussions that took place at EMIM2022. Procedures The survey was delivered to the community by the ESMI office and was promoted through the Society channels, email lists and webpages. The survey contained seven sections organised as generic questions and imaging modality-specific questions. The generic questions focused on issues regarding data acquisition, data processing, data storage, publishing and community awareness of international guidelines for animal research. Specific questions on practices in optical imaging, PET, CT, SPECT, MRI and ultrasound were further included. Results Data from the STANDARD survey showed that 47% of survey participants do not have or do not know if they have QC/QA guidelines at their institutes. Additionally, a large variability exists in the ways data are acquired, processed and reported regarding general aspects as well as modality-specific aspects. Moreover, there is limited awareness of the existence of international guidelines on preclinical (imaging) research practices. Conclusions Standardisation of preclinical imaging techniques remains a challenge and hinders the transformative potential of preclinical imaging to augment biomedical research pipelines by serving as an easy vehicle for translation of research findings to the clinic. Data collected in this project show that there is a need to promote and disseminate already available tools to standardise preclinical imaging practices.

show abstract

“…It was estimated that more than 100 million laboratory animals were sacrificed for biomedical research annually ( Taylor and Alvarez, 2019 ). Therefore, William Russel and Rex Burch proposed the 3Rs principle (replacement, reduction, and refinement) in 1959 ( Vitale et al, 2009 ; Wachsmuth et al, 2021 ), attempting to reduce animal use. The 2010 EU Directive states that animals have intrinsic values that need to be respected and that animal experiments should be carefully evaluated in biomedical research, with animal welfare considerations a top priority.…”

Section: Introductionmentioning

confidence: 99%

Application of Physiologically Based Pharmacokinetic Modeling in Preclinical Studies: A Feasible Strategy to Practice the Principles of 3Rs

Yuan

Zhang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Pharmacokinetic characterization plays a vital role in drug discovery and development. Although involving numerous laboratory animals with error-prone, labor-intensive, and time-consuming procedures, pharmacokinetic profiling is still irreplaceable in preclinical studies. With physiologically based pharmacokinetic (PBPK) modeling, the in vivo profiles of drug absorption, distribution, metabolism, and excretion can be predicted. To evaluate the application of such an approach in preclinical investigations, the plasma pharmacokinetic profiles of seven commonly used probe substrates of microsomal enzymes, including phenacetin, tolbutamide, omeprazole, metoprolol, chlorzoxazone, nifedipine, and baicalein, were predicted in rats using bottom-up PBPK models built with in vitro data alone. The prediction’s reliability was assessed by comparison with in vivo pharmacokinetic data reported in the literature. The overall predicted accuracy of PBPK models was good with most fold errors within 2, and the coefficient of determination (R2) between the predicted concentration data and the observed ones was more than 0.8. Moreover, most of the observation dots were within the prediction span of the sensitivity analysis. We conclude that PBPK modeling with acceptable accuracy may be incorporated into preclinical studies to refine in vivo investigations, and PBPK modeling is a feasible strategy to practice the principles of 3Rs.

show abstract

Contribution of preclinical MRI to responsible animal research: living up to the 3R principle

Cited by 11 publications

References 18 publications

Pharmacokinetics of Novel Furoxan/Coumarin Hybrids in Rats Using LC-MS/MS Method and Physiologically Based Pharmacokinetic Model

Pharmacokinetics of Novel Furoxan/Coumarin Hybrids in Rats Using LC-MS/MS Method and Physiologically Based Pharmacokinetic Model

Community Survey Results Show that Standardisation of Preclinical Imaging Techniques Remains a Challenge

Application of Physiologically Based Pharmacokinetic Modeling in Preclinical Studies: A Feasible Strategy to Practice the Principles of 3Rs

Contact Info

Product

Resources

About