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Figure 1 | BMC Systems Biology

Figure 1

From: A systems biology approach to dynamic modeling and inter-subject variability of statin pharmacokinetics in human hepatocytes

Figure 1

Scheme of the full model of Atorvastatin metabolism in primary human hepatocytes. The scheme illustrates atorvastatin metabolic and transport pathways in human hepatocytes. The model comprises the active import and export of AS and ASL, and corresponding para- and ortho-hydroxy-metabolites, ASpOH and ASoOH, ASLpOH and ASLoOH, mediated by import proteins, OATP1B1 and OATP2B1 (solid lines), and export proteins, MDR1 and MRP2 (solid lines), as well as passive diffusion steps (dashed lines). AS and ASL are hydroxylated to the corresponding metabolites by CYP3A4, respectively (solid lines). Compound AS is converted via an instable glucuronid-intermediate to ASL mediated by UGT1A3 (solid lines). The lactones are hydrolyzed either chemically or enzymatically by putative PON to the respective acids (solid and dotted line). Acids and lactones are further subject to unspecific binding to macromolecules in human hepatocytes (dashed lines).

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