Fig 1.
Chromatograms of tramadol and its metabolites in koala plasma.
A) blank koala plasma; B) blank plasma spiked with tramadol, M1, and M2 (all at a concentration of 62.5 ng/mL); C) male koala plasma 2h after 4 mg/kg tramadol administration; D) female koala plasma 2 h after 4 mg/kg tramadol administration. Additional unidentified metabolites can be seen in C and D.
Fig 2.
Median (with error) tramadol plasma concentrations vs. time curves when administered at 2 mg/kg, s.c. (n = 2) and 4 mg/kg, s.c. (n = 4).
Dotted line signifies suggested tramadol minimally effective plasma concentration in humans of 100 ng/mL [24]. The graph of the 4 mg/kg tramadol dose dips slightly below the 2 mg/kg tramadol dose–this may be due to individual variability between koalas.
Fig 3.
Median (with error) semi-log tramadol plasma concentration versus time when administered at 2 mg/kg, s.c. (n = 2) and 4 mg/kg, s.c. (n = 4).
Dotted line signifies tramadol minimally effective plasma concentration of 100 ng/mL [24]. The graph of the 4 mg/kg tramadol dose dips slightly below the 2 mg/kg tramadol dose–this may be due to individual variability between koalas. The tramadol concentrations of the 4 mg/kg tramadol dose at not provided at 12 h as they are below the LLOQ = 15.63 ng/mL.
Fig 4.
Median (with error) semi-log M1 plasma concentrations vs. time curves when administered at 2 mg/kg, s.c. (n = 2) and 4 mg/kg, s.c. (n = 4).
Dotted line signifies suggested M1 minimally effective plasma concentration in humans of 36 ng/mL [24].
Table 1.
Pharmacokinetic indices of tramadol when administered at 2 mg/kg, and 4 mg/kg, both administered by s.c. injection.
Table 2.
Pharmacokinetic indices of M1 when tramadol was administered at 2 mg/kg, and 4 mg/kg both administered by s.c. injection.
Table 3.
Pharmacokinetic indices of M2 when tramadol was administered at 2 mg/kg, and 4 mg/kg, both administered by s.c. injection.
Table 4.
Comparison of tramadol parameters and M1 half-life (mean ± SD [range]) between species.