TABLE 3

Plasma concentrations (nanograms per milliliter) of tramadol, M1, M2, and M5 and their respective conjugates measured 1 hour after oral administration of tramadol (5 mg/kg b.wt.) to 11 dogs (twice), and after pretreatment with fluconazole and placebo, separated by a 2-week washout period

Conjugate concentrations are given as mass equivalents of the respective parent (unconjugated) compound. The data are presented as the median and the 25%–75% interquartile range of concentrations, and as the GMR and 90% confidence interval. The P value indicates the significance of paired comparisons between fluconazole and placebo treatments using the Wilcoxon signed-rank test.

AnalytePlasma Concentration (ng/ml)Plasma Concentration Ratio
PlaceboFluconazole(Fluconazole/Placebo)
Median25%–75%Median25%–75%P ValueGMR90% CI
T0.0(0.0–3.8)3.0(0.0–305)0.116.6(1.1–40)
T conj.0.0(0.0–0.0)0.0(0.0–13)0.0943.7(1.1–12)
M10.0(0.0–0.0)2.3(0.0–77)0.047*6.1(1.7–21)
M1 conj.2.5(0.0–7.7)0.0(0.0–191)0.911.2(0.25–5.5)
M20.0(0.0–47)0.0(0.0–6.7)0.310.51(0.12–2.1)
M2 conj.1.1(0.0–5.8)0.0(0.0–1.3)0.150.41(0.15–1.1)
M53.9(0.0–81)0.0(0.0–8.9)0.0780.25(0.069–0.92)
M5 conj.7.5(1.6–169)0.0(0.0–14)0.130.12(0.025–0.57)
  • CI, confidence interval; conj., conjugate; T, tramadol.

  • * A P value of less than 0.05 is considered statistically significant.