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. 2014 Sep 30;6(11):1398–1422. doi: 10.15252/emmm.201404168

Figure 12. Plasma and tissue concentrations of R-flurbiprofen in C57BL6/J and SJL mice and pharmacodynamic effects in terms of prostaglandins and endocannabinoids.

Figure 12

  1. Plasma concentration versus time courses in C57BL6/J mice (n = 14) after a single oral dose of 10 mg/kg R-flurbiprofen. The rates of R to S inversion in (A) and (B) were calculated on the basis of the AUCs up to 8 h.
  2. Comparison of the circadian rhythms of R- and S-flurbiprofen plasma concentrations in C57BL6/J and SJL mice receiving continuous R-flurbiprofen (10 mg/kg/day) in the drinking water (n = 5 per group).
  3. Tissue concentrations of R-and S-flurbiprofen in C57BL6/J mice in liver, skin and three brain regions (PFC, prefrontal cortex; Hippo, hippocampus) 7 h after a single oral dose of 10 mg/kg R-flurbiprofen (n = 14).
  4. Prostaglandin concentrations in the spinal cord of C57BL6/J mice in the EAE model. The mice received preventive treatment with vehicle, R-flurbiprofen (2.5, 5, 10 mg/kg/day), S-flurbiprofen (10 mg/kg/day) or FTY (0.5 mg/kg/day) from the 3rd day after immunization, and the tissue was dissected out during the flare of the disease, day 20. (n = 6 per group, two-way ANOVA (‘lipid’ and ‘treatment’) with subsequent Dunnett post hoc analyses versus vehicle. P-values of post hoc tests PGE2: *10.0014, *20.0002, *30.0013, *40.0004, *50.0001; PGD2: *10.0275, *20.050, *30.0001; TXB2: *10.0405, *20.0351, *30.0024; PGF2α: *10.0395, *2 0.0172; 6ketoPGF1α: *10.0440, *20.0428, *30.0001).
  5. Endocannabinoid concentrations in plasma of C57BL6/J mice before and after receiving a single i.p. injection of 10 mg/kg R-flurbiprofen during the flare of EAE (n = 5). rm-ANOVA within subject factor ‘time’ for AEA P = 0.0061, OEA P = 0.0001, PEA P = 0.0010, 2-AG 0.0016. The asterisks indicate those time points that differed significantly versus baseline.
  6. Endocannabinoid concentrations in the somatosensory cortex (SSC) of naïve and EAE mice (C57BL6/J) treated continuously with vehicle or R-flurbiprofen (10 mg/kg/day in drinking water) from the 3rd day after immunization (n = 13 per group). The tissue was dissected out during the flare of the disease, day 20 (univariate ANOVA with post hoc Bonferroni for AEA: *P = 0.020; OEA: *P = 0.000052; PEA: *P = 0.000412; 2-AG: *1P =0.0002, *2P = 0.00003).

Data information: Abbreviations in (E) and (F): AEA, anandamide; OEA, oleoylethanolamide; PEA, palmitoylethanolamide; 2-AG arachidonoylethanolamide.