Search bioRxiv⌕ Search

Biology subjects

Konietschke, F.

Publications and source records attributed to Konietschke, F..

2 recordsLinked to original sources

Multi-Lab Testing of Early Preclinical Discoveries Identifies Promising Treatments

A fundamental challenge in drug development is the frequent failure of early laboratory research to translate into clinical benefit. One promising solution is to confirm findings from exploratory single-laboratory studies across multiple laboratories before clinical testing. We investigated this approach following the conduct of preclinical multi-laboratory studies across different fields of medicine. For this, we evaluated effect sizes, experimental rigor, and a set of criteria to identify determinants of confirmation success. When tested under increased rigor, only a fraction of multi-laboratory studies confirmed the initial results. The underlying effect size reduction was associated with outcome-relevant experimental differences between exploratory and confirmatory stages. In summary, multi-laboratory studies proved highly informative and served as an effective filter for promising treatments.

scientific communication and education↗

A Buprenorphine depot formulation provides effective sustained post-surgical analgesia for 72h in mouse femoral fracture models

Adequate pain management is essential for ethical and scientific reasons in animal experiments and should completely cover the period of expected pain without the need for frequent re-application. However, current depot formulations of Buprenorphine are only available in the USA and have limited duration of action. Recently, a new microparticulate Buprenorphine formulation (BUP-Depot) for sustained release has been developed as an alternative product within Europe. Pharmacokinetics indicate a potential effectiveness for about 72h. Here, we investigated whether the administration of the BUP-Depot ensures continuous and sufficient analgesia in two mouse femoral fracture models and could therefore serve as a potent alternative to the application of Tramadol via drinking water. Both protocols were examined for analgesic effectiveness, side effects on experimental readout, and effects on fracture healing outcomes in male and female C57BL/6N mice. The BUP-Depot provided effective analgesia for 72h, comparable to the effectiveness of Tramadol in drinking water. Fracture healing outcome was not different between analgesic regimes. The availability of a Buprenorphine depot formulation for laboratory animals in Europe would be a beneficial addition for extended pain relief in mice, thereby increasing animal welfare.

animal behavior and cognition↗