Christian Schnell describes his work involving implantable infusion pump studies in rodents and the advancement of pharmacological interventions in oncology research.
In oncology drug discovery programs, modulating target engagement via drug-delivery technologies can enable pivotal pharmacological studies. Over the past decade, there is increasing interest in establishing a robust mechanistic understanding of the pharmacokinetics–pharmacodynamics (PK–PD) relationship of a given compound and its connection to the anti-tumor efficacy profile.
In this webinar, Christian will describe the validation studies performed in his pharmacology unit with iPRECIO pumps implanted in rats and mice. Accurate PK-PD assessment and corresponding antitumor activity were assessed among several drug discovery programs. He provides evidence that the investigation of such compound specific relationships are a pre-requisite for the planning of meaningful efficacy studies in preclinical models and the subsequent translation into patient’s clinical trials.
Taking into account best practices and the 3Rs of animal research (Reduction, Refinement and Replacement), implantable pumps are one of the most effective ways to deliver drugs without interfering with normal animal activity, especially in a group-housed environment. Long term, chronic dosing regimens and quantitative pharmacology for PK-PD may be scheduled and executed with minimal human intervention and animal stress, and in doing so reducing the impact of these important confounding factors. Therefore, data variability will be lower leading to reduction of animal use. Moreover, it should be emphasized that the simultaneous use of complementary novel technologies within the same animal (like radio-telemetry and programmable pumps as described here) will enable advances in the understanding of complex physiological regulation mechanism following pharmacological intervention, possibly leading to improved therapies in the clinic.
Associate Director Oncology NIBR
Novartis in Basel