Table 2.
Estimated non-compartmental pharmacokinetic parameters (mean ± SD) based on time vs. plasma flunixin and 5-OH concentration profiles after single (trial 3) and multiple (trial 4) doses of flunixin meglumine administered intravenously (IV) and subcutaneous (SC) at 1.1 mg/kg to eight healthy lactating dairy does.
| Trial 3 | Trial 3 | Trial 4 | Trial 4 | ||
|---|---|---|---|---|---|
| Parent drug or metabolite | PK parameter | Mean ± SD (IV) | Mean ± SD (SC) | Mean ± SD (IV) | Mean ± SD (SC) |
| Flunixin | Cmax (μg/ml) | 7.2346 ± 3.3252 | 0.8383 ± 0.2372 | 7.6909 ± 1.3452 | 1.4341 ± 0.2237 |
| Tmax (h) | NA | 1.28 ± 0.31 | NA | 1.17 ± 0.44 | |
| T1/2Z (h) | 4.56 ± 2.70 | 3.77 ± 5.69 | 4.35 ± 2.43 | 3.03 ± 1.57 | |
| Z (h−1) | 0.122 ± 0.08 | 0.11 ± 0.13 | 0.13 ± 0.08 | 0.19 ± 0.09 | |
| AUCinf (h*μg/ml) | 4.319 ± 1.350 | 3.059 ± 0.619 | 6.335 ± 0.993 | 5.672 ± 1.185 | |
| AUC%ext (%) | 0.28 ±0.27 | 0.28 ± 0.26 | 0.057 ± 0.16 | 0.035 ± 0.053 | |
| Vz, Vz/F (ml/kg) | 1,945 ± 1,357 | 2,518 ± 3,295 | 1,222 ± 611 | 939 ± 499 | |
| Cl, CL/F (ml/kg/h) | 265 ± 78.4 | 365 ± 59.1 | 176 ± 29.4 | 199 ± 57.8 | |
| AUMCinf (h*h*μg/ml) | 7.842 ± 1.767 | 11.790 ± 1.903 | 15.971 ± 6.142 | 22.503 ± 8.551 | |
| MRTinf (h) | 1.83 ± 0.62 | 3.88 ± 0.61 | 2.38 ± 1.03 | 3.99 ± 0.86 | |
| Ebody | 3.55 ± 1.00 | – | – | – | |
| F (%) | – | 74.0 ± 20.0 | – | – | |
| 5-OH | Cmax (μg/ml) | 0.1341 ± 0.0245 | 0.0552 ± 0.0185 | 0.1385 ± 0.0343 | 0.0605 ± 0.0153 |
| Tmax (h) | 0.25 ± 0.18 | 1.33 ± 0.42 | 0.19 ± 0.04 | 1.65 ± 0.26 | |
| T1/2Z (h) | 3.65 ± 3.24 | 3.34 ± 1.05 | 3.68 ± 5.43 | 2.99 ± 3.23 | |
| Z (h−1) | 0.14 ± 0.09 | 0.19 ± 0.08 | 0.12 ± 0.09 | 0.16 ± 0.14 | |
| AUCinf (h*μg/ml) | 0.2216 ± 0.0408 | 0.2372 ± 0.0673 | 0.2170 ± 0.0564 | 0.2631 ± 0.0780 | |
| Vz, Vz/F (ml/kg) | 30,209 ± 22,990 | 24,200 ± 10,441 | 32,388 ± 38,001 | 22,395 ± 34,303 | |
| Cl, CL/F (ml/kg/h) | 5,034 ± 894 | 4,785 ± 1,229 | 5,205 ± 1,196 | 4,384 ± 1,818 | |
| AUMCinf (h*h*μg/ml) | 0.745 ± 0.251 | 1.007 ± 0.233 | 0.694 ± 0.306 | 1.129 ± 0.487 | |
| MRTinf (h) | 3.34 ± 0.90 | 3.34 ± 0.89 | 3.10 ± 1.08 | 4.36 ± 1.13 |
AUCinf, area under the concentration curve from time 0 to infinity; AUC%ext (%), area under the concentration curve extrapolated; AUMCinf, area under the moment curve from time zero to infinity; Cmax, maximum concentration observed; CL, observed clearance; MRTinf, mean residence time; Ebody, Extraction ratio; F, bioavailability; T1/2Z, half-life of terminal elimination; Tmax, observed time to maximum concentration; Vz, volume of distribution; Z, terminal elimination constant.
Trial 3: Lactating dairy does (n = 8). Trial 4: Lactating dairy does (n = 8).