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. 2019 Aug 13;9:11740. doi: 10.1038/s41598-019-47876-0

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© The Author(s) 2019

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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Schematic presentation of a population pharmacokinetic model. Compartments: gastrointestinal tract (GI, 1, 4), central compartment for tacrolimus (2), peripheral compartment for tacrolimus (3), central compartment for mycophenolic acid (5), peripheral compartment for mycophenolic acid (6), compartment for mycophenolic acid 7-O-glucuronide (7), compartment for gall bladder (8), compartment for mycophenolic acid acyl glucuronide (9). TAC, tacrolimus; K_a, absorption rate constant; k₂₃, k₃₂, k₅₆, and k₆₅, intercompartment rate constants; CL, clearance; MPA, mycophenolic acid; MPAG, MPA 7-O-glucuronide; AcMPAG, MPA acyl glucuronide; k₅₇ and k₅₉, metabolized rate constants for mycophenolic acid; EHC, enterohepatic circulation; k₇₈, biliary recirculation of MPAG into GI; k₇₀ and k₉₀, eliminated rate constants; k₈₄, gallbladder emptying rate constant; Meal times were used to trigger timing of gall bladder emptying.