TABLE 4

Plasma concentrations (nanograms per milliliter) of tramadol (T), M1, M2, and M5 and their respective conjugates measured 4 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
T6.4(3.0–20)215(59–502)<0.001*32(11–98)
T conj.0.0(0.0–5.5)13(0.0–57)0.135.8(0.79–42)
M10.0(0.0–2.8)54(38–68)<0.001*40(21–76)
M1 conj.34(13–67)325(121–764)<0.001*12(5.8–24)
M283(33–215)5.4(1.1–18)0.002*0.083(0.033–0.21)
M2 conj.8.8(0.0–40.9)2.2(0.0–3.8)0.049*0.22(0.061–0.82)
M579(40–88)10(5.7–12)0.005*0.27(0.094–0.79)
M5 conj.825(497–1195)54(21–109)0.002*0.12(0.042–0.32)
  • CI, confidence interval; conj., conjugate; T, tramadol.

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