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Published Erratum
. 2021 Jan:183:114306.
doi: 10.1016/j.bcp.2020.114306. Epub 2020 Nov 5.

Corrigendum to "In vitro to in vivo extrapolation of the complex drug-drug interaction of bupropion and its metabolites with CYP2D6; simultaneous reversible inhibition and CYP2D6 downregulation" [Biochem. Pharmacol. 123(2017)85-96]

Jennifer E Sager  1 , Sasmita Tripathy  1 , Lauren S L Price  1 , Abhinav Nath  2 , Justine Chang  3 , Alyssa Stephenson-Famy  3 , Nina Isoherranen  4
Affiliations
Published Erratum

Corrigendum to "In vitro to in vivo extrapolation of the complex drug-drug interaction of bupropion and its metabolites with CYP2D6; simultaneous reversible inhibition and CYP2D6 downregulation" [Biochem. Pharmacol. 123(2017)85-96]

Jennifer E Sager et al. Biochem Pharmacol. 2021 Jan.
No abstract available

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Figures

Figure 4.
Figure 4.. Effects of bupropion and its metabolites on CYP2D6 and SHP mRNA in HepG2 cells.
CYP2D6 mRNA levels in HepG2 cells exposed to multiple concentrations of (A) erythrohydrobupropion, (B) threohydrobupropion, (C) R,R-OH-bupropion, (D) bupropion and (E) S, S-OH-bupropion are shown. The points show the measured effect with its standard deviation and the line shows the fit of equation 2, E=E0−Emax×[I]EC50+[I] to the data. For R,R-OH-bupropion solubility limitations prevent measurement of dose–response relationship and hence the line shows the fit of equation 3, E = Eo – slope × [I] to the data. Panel F shows the fold change in SHP mRNA levels in HepG2 cells following 72 h of treatment with bupropion (bup 0.5 μM, 2.5 μM, 5 μM), R,R-OH-bupropion (R,R-OH, 5 μM, 25 μM, 50 μM), S,S-OH-bupropion (S,S-OH 0.5 μM, 2.5 μM, 5 μM), erythrohydrobupropion (erythro 0.5 μM, 2.5 μM, 5 μM) or threohydrobupropion (threo 2 μM, 10 μM, 20 μM). The data are shown as mean of three replicates and the standard deviation is shown as the error bar.
Figure 5.
Figure 5.. CYP2D6 specific downregulation of mRNA expression by bupropion and its metabolites in plated human hepatocytes.
Fold change in (a) CYP2D6, (b) CYP3A4 and (c) CYP1A2 mRNA expression in comparison to vehicle treated controls following 72 h treatment of plated human hepatocytes from three donors with erythrohyrobupropion (Erythro), threohydrobupropion (Threo), R,R-OH-bupropion (R,R-OH) or S,S-OH-bupropion (S,S-OH) bupropion (Bup), and mixture of all compounds at concentrations approximately 5 times steady state concentrations as described in methods section. All experiments were conducted in triplicate and the standard deviation is shown as the error bar.
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