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. 2020 Jun 22;117(27):16009–16018. doi: 10.1073/pnas.1920483117

Fig. 6.

Fig. 6.

Interactions between the gut microbiota, azo dye excipients, and drug absorption in CONV-R and gnotobiotic mice. (A and B) Recovery of residual FD&C Red No. 40 dye in fecal collections over 24 h. (A) CONV-R, germ-free (GF), and gnotobiotic mice were orally dosed with 5 mg of FD&C Red No. 40 (∼250 mg/kg; n = 3 to 8 mice per group). CONV-R mice without dye are also included as a control (n = 3). Bottom 3 indicates mice colonized with the three worst FD&C Red No. 40 metabolizers: B. bifidum ADE2, B. pseudocatenulatum ADE4, and B. adolescentis ADE1. Top 3 indicates mice colonized with the best 3 FD&C Red No. 40 metabolizers: F. pleomorphus ADE20, C. hylemonae ADE14, and C. ramosum ADE26. (B) Fecal FD&C Red No. 40 dye levels in CONV-R mice depend upon oral dose (n = 3 mice per group). (C and D) Total colonization is significantly higher in the (C) cecum and (D) stool of CONV-R mice relative to both gnotobiotic groups. (E) Plasma concentration–time profiles of fexofenadine after oral administration of 15 mg/kg fexofenadine plus saline (blue circles, n = 10), 2.5 mg/kg FD&C Red No. 40 (green squares, n = 6), or 25 mg/kg FD&C Red No. 40 (red triangles, n = 9) to Pgp-deficient (mdr1a/b−/−) germ-free mice. Each point represents the mean ± SEM. (F–H) Pharmacokinetic parameters calculated using Phoenix WinNonlin v8.1: (F) plasma fexofenadine AUC0–120min, (G) plasma fexofenadine AUC0–360min, and (H) maximum plasma concentration (Cmax). Each point represents the data from an individual mouse administered with 15 mg/kg fexofenadine plus saline (blue; n = 10), 2.5 mg/kg FD&C Red No. 40 (green; n = 6), or 25 mg/kg FD&C Red No. 40 (red; n = 9). Statistics: (A, C, and D) ANOVA with Tukey’s correction, **P < 0.01, ***P < 0.001; (B and F) unpaired Student’s t test, *P < 0.05, **P < 0.01. The reported contrasts in A are relative to CONV-R mice either with or without dye administration.