A physiologically based pharmacokinetic model for V937 oncolytic virus in mice

Introduction: Oncolytic viruses (OVs) represent a novel therapeutic strategy in oncology due to their capability selectively infect and replicate cancer cells, triggering direct and/or immune-induced tumor lysis. However, the mechanisms governing OV pharmacokinetics are still poorly understood. This work aims develop physiologically based pharmacokinetic model of OV, V937, non-tumor-bearing mice get quantitative understanding its elimination tissue uptake processes. Materials methods: Model development was performed using data obtained from 60 mice. Viral levels were quantified eight tissues after single intravenous V937 dose. An external dataset used for validation. test set included multiple-dose experiments with different routes administration. distribution each organ described physiological structure on mouse-specific blood flows volumes. Analyses non-linear mixed-effects approach NONMEM 7.4. Results: showed drop 10 8 5 copies/µg RNA at day 1 blood, reflected high estimate total clearance (18.2 mL/h). A well-stirred provided an adequate description all organs except muscle heart, where saturable process improved description. The highest numbers viral copies observed brain, lymph node, kidney, liver, lung, spleen first injection. On other hand, maximum amount muscle, pancreas occurred 3 days Conclusion: To best our knowledge, this is developed characterize biodistribution, representing relevant source knowledge regarding vivo behavior OVs. can be further expanded by adding compartment, OVs could replicate.