Expansion of platform physiologically-based pharmacokinetic model for monoclonal antibodies towards different preclinical species: cats, sheep, and dogs.

Autor: Huang HW; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, 455 Pharmacy Building, Buffalo, NY, 14214-8033, USA., Wu S; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, 455 Pharmacy Building, Buffalo, NY, 14214-8033, USA., Chowdhury EA; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, 455 Pharmacy Building, Buffalo, NY, 14214-8033, USA., Shah DK; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, 455 Pharmacy Building, Buffalo, NY, 14214-8033, USA. dshah4@buffalo.edu.
Jazyk: angličtina
Zdroj: Journal of pharmacokinetics and pharmacodynamics [J Pharmacokinet Pharmacodyn] 2024 Dec; Vol. 51 (6), pp. 621-638. Date of Electronic Publication: 2023 Nov 10.
DOI: 10.1007/s10928-023-09893-5
Abstrakt: Monoclonal antibodies (mAbs) are becoming an important therapeutic option in veterinary medicine, and understanding the pharmacokinetic (PK) of mAbs in higher-order animal species is also important for human drug development. To better understand the PK of mAbs in these animals, here we have expanded a platform physiological-based pharmacokinetic (PBPK) model to characterize the disposition of mAbs in three different preclinical species: cats, sheep, and dogs. We obtained PK data for mAbs and physiological parameters for the three different species from the literature. We were able to describe the PK of mAbs following intravenous (IV) or subcutaneous administration in cats, IV administration in sheep, and IV administration dogs reasonably well by fixing the physiological parameters and just estimating the parameters related to the binding of mAbs to the neonatal Fc receptor. The platform PBPK model presented here provides a quantitative tool to predict the plasma PK of mAbs in dogs, cats, and sheep. The model can also predict mAb PK in different tissues where the site of action might be located. As such, the mAb PBPK model presented here can facilitate the discovery, development, and preclinical-to-clinical translation of mAbs for veterinary and human medicine. The model can also be modified in the future to account for more detailed compartments for certain organs, different pathophysiology in the animals, and target-mediated drug disposition.
Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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