![]() ![]() One such PBPK model for mAbs can simultaneously characterize the disposition data obtained from various published mAb PBPK models, and it is also capable of characterizing mAb disposition in various preclinical species and human simultaneously. The intricacy of PBPK models enables detailed quantitative assessment of the plasma and tissue disposition of drugs, and facilitates scale-up of the model to different species because the structural model is relatively common to most mammalian species. Use of a physiologically-based pharmacokinetic (PBPK) model is an alternative to performing cumbersome in vivo biodistribution studies. For mAbs, the tissue distribution is usually investigated by performing biodistribution studies with radiolabeled molecules, but such studies are labor intensive, costly, and require large numbers of animals. It thus becomes important to characterize and accurately predict the tissue distribution of the molecule to better understand the dose-response relationship. It can also help eliminate or optimize biodistribution studies, and interpret efficacy or toxicity of the drug in a particular tissue.įor many monoclonal antibodies (mAbs) and other targeted drug modalities, the molecular target may be located within tissues, making their pharmacodynamic (PD) and exaggerated-PD/toxic effects a function of tissue concentrations. The use of ABC to infer tissue concentrations of mAbs and related molecules provides a valuable tool for investigating preclinical or clinical disposition of these molecules. The validity of using the ABC to predict mAb concentrations in different tissues of mouse, rat, monkey, and human species was evaluated by generating validation data sets, which demonstrated that predicted concentrations were within 2-fold of the observed concentrations. Estimated ABC values suggest that typically the concentration of mAb in lung is 14.9%, heart 10.2%, kidney 13.7%, muscle 3.97%, skin 15.7%, small intestine 5.22%, large intestine 5.03%, spleen 12.8%, liver 12.1%, bone 7.27%, stomach 4.98%, lymph node 8.46%, adipose 4.78%, brain 0.351%, pancreas 6.4%, testes 5.88%, thyroid 67.5% and thymus is 6.62% of the plasma concentration. The relationship between the plasma and various tissue concentrations was mathematically characterized using the antibody biodistribution coefficient (ABC). The hypothesis was verified for various tissues in mice, rat, monkey, and human using mAb or antibody-drug conjugate tissue distribution data collected from diverse literature. Based on the profiles, we hypothesized that a linear relationship between the plasma and tissue concentrations of non-binding mAbs could exist and that the relationship may be generally constant irrespective of the absolute mAb concentration, time, and animal species being analyzed. plasma concentration profiles have been generated from a physiologically-based pharmacokinetic model of monoclonal antibody (mAb). I climbed Mount Fuji, ate gelato by the Coliseum in Rome, and sailed high above the rooftops aboard the London Eye.Tissue vs. Modeling helped me pay for courses at McGill University and allowed me to travel the world. When I was 17, a modeling scout approached me at a mall. But events like these are common - I’m tempted to say normal - for young models working overseas. I would like to tell you that this day was unusual. She started to cry on the set, and when the photographer complained to our agents, the agency hastily discounted the model’s fee. She had just returned from a photoshoot where the photographer was touching her inappropriately. Her English wasn’t great, and she mainly talked to the other Russian girls, but through a friend, she told her story. ![]() But one of our crew wasn’t happy: She was a model from Russia, 15 years old, sitting alone and looking down at the floor. Iced lattes cool us down from the oppressive Shanghai heat, and the cheerful, air-conditioned interior serves as welcome relief from an afternoon of monotonous castings.
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