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. 2017 Dec 14;7:17560. doi: 10.1038/s41598-017-17692-5

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© The Author(s) 2017

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Illustration of the parallelogram approach for inter-species extrapolation of AUC of a reactive metabolite in human using in vitro metabolic data. For a metabolic transformation of R to RX, AUC-RX and AUC-R refer to the in vivo dose of RX and R, respectively, and EE-R → RX and EE-RX_el refer to the in vitro enzyme efficiency for metabolic transformation of R to RX and elimination of RX, respectively.