Table 1.
Non-compartmental pharmacokinetic parameters (mean, SD) of flunixin and 5-hydroxy flunixin (5-OH) after a single intravenous (IV) and subcutaneous (SC) flunixin meglumine dose (1.1 mg/kg) administered to non-lactating dairy does.
| Trial 1 | Trial 1 | Trial 2 | Trial 2 | ||
|---|---|---|---|---|---|
| Parent drug or metabolite | PK parameter | Mean ± SD (IV) | Mean ± SD (SC) | Mean ± SD (IV) | Mean ± SD (SC) |
| Flunixin | Cmax (μg/ml) | 9.972 ± 2.596 | 2.182 ± 0.255 | 9.613 ± 2.737 | 2.495 ± 1.234 |
| Tmax (h) | NA | 1.41 ± 0.38 | NA | 0.90 ± 0.42 | |
| T1/2Z (h) | 2.17 ± 2.07 | 4.08 ± 22.5 | 3.13 ± 2.26 | 2.87 ± 3.89 | |
| Z (h−1) | 0.21 ± 0.24 | 0.06 ± 0.17 | 0.18 ± 0.09 | 0.15 ± 0.15 | |
| AUCinf (h*μg/ml) | 9.880 ± 2.327 | 8.806 ± 1.762 | 6.429 ± 2.187 | 5.780 ± 1.828 | |
| AUC%ext (%) | 0.017 ± 0.072 | 0.12 ± 6.38 | 0.025 ± 0.062 | 0.023 ± 0.078 | |
| Vz, Vz/F (ml/kg) | 444 ± 303 | 1,071 ± 2,978 | 903 ± 594 | 1,001 ± 1,634 | |
| Cl, CL/F (ml/kg/h) | 114.0 ± 24.4 | 127 ± 26.4 | 182 ± 83.7 | 199 ± 75.5 | |
| AUMCinf (h*h*μg/ml) | 27.205 ± 15.539 | 51.310 ± 116.135 | 11.710 ± 5.056 | 17.222 ± 7.269 | |
| MRTinf (h) | 2.74 ± 0.80 | 5.07 ± 9.48 | 1.91 ± 0.03 | 3.03 ± 0.77 | |
| Ebody | 1.44 ± 0.29 | – | 2.08 ± 0.98 | – | |
| F (%) | – | 89.0 ± 5.0 | – | 94.0 ± 3.3 | |
| 5-OH | Cmax (μg/ml) | 0.1006 ± 0.0203 | 0.0493 ± 0.0143 | 0.1476 ± 0.0539 | 0.0668 ± 0.0267 |
| Tmax (h) | 0.23 ± 0.45 | 1.55 ± 0.35 | 0.16 ± 0.09 | 1.08 ± 0.42 | |
| T1/2Z (h) | 4.18 ± 1.1 | 5.41 ± 6.88 | 3.64 ± 2.47 | 3.67 ± 3.87 | |
| Z (h−1) | 0.16 ± 0.04 | 0.09 ± 0.05 | 0.15 ± 0.09 | 0.14 ± 0.1 | |
| AUCinf (h*μg/ml) | 0.244 ± 0.083 | 0.243 ± 0.072 | 0.241 ± 0.080 | 0.208 ± 0.056 | |
| Vz, Vz/F (ml/kg) | 29,190 ± 13,876 | 43,015 ± 41,692 | 28,131 ± 21,109 | 33,595 ± 30,352 | |
| Cl, CL/F (ml/kg/h) | 4,718 ± 1,393 | 4,665 ± 1,395 | 4,792 ± 1,678 | 5,549 ± 2,755 | |
| AUMCinf (h*h*μg/ml) | 1.013 ± 0.533 | 1.547 ± 1.237 | 0.700 ± 0.339 | 0.835 ± 0.342 | |
| MRTinf (h) | 4.25 ± 1.01 | 6.31 ± 2.48 | 2.94 ± 0.78 | 4.09 ± 1.27 |
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 1 consisted of 8 healthy pregnant non-lactating does. Trial 2 consisted of 20 nulliparous non-lactating does.