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. 2020 Oct 1;10:16268. doi: 10.1038/s41598-020-73255-1

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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PK prediction using kinetic parameters obtained from in vivo and in vitro cell-based assays. (a) PK model for simulating concentration–time profiles of the antibody. A 2-compartment model with the Michaelis–Menten equation was used for PK prediction. The in vitro V_max was scaled by the number of target-expressing cells per whole liver, and the velocity per body weight was then calculated using the body weight of the mice. C: concentrations of the antibody. (b) Predicted and observed concentration–time profile of the antibody in mice at doses of 1 mg/kg (white triangle), 3 mg/kg (black triangle), 10 mg/kg (white square), 30 mg/kg (black circle), and 100 mg/kg (white circle). The solid line shows the simulated PK profile using in vitro parameters, and the dots show the observed concentrations. Each point represents the mean ± SD (n = 3). (c) The relationship between predicted and observed concentrations. (d) The relationship between predicted and observed AUC_0–inf. The solid lines show the lines of unity, and the area between the dotted lines represents an area within a threefold difference.