Pharmacokinetics and effect on renal function and average daily gain in lambs after castration and tail docking, of firocoxib and meloxicam

Figures & data

Figure 1. Least square mean (±SE) concentration of firocoxib in plasma after IM (dotted line; 1 mg/kg) and oral (solid line; 1 mg/kg) administration to unweaned lambs (n = 15 lambs per group) undergoing hot-iron tail docking and rubber ring castration. Asterisks indicate that the mean values for the two routes of administration differed (p < 0.05) at 1, 6 and 8 hours after administration.

Figure 2. Least square mean (±SE) plasma concentrations of meloxicam after IM (1 mg/kg) administration to unweaned lambs (n = 15 lambs) undergoing hot-iron tail docking and rubber ring castration.

Table 1. Least squares mean (±SE)^a pharmacokinetic parameters of firocoxib and meloxicam following oral or IM administration to lambs (n = 15, 3–6 weeks old) at a dose of 1 mg/kg.

Pharmacokinetic parameter	Firocoxib (IM)	Firocoxib (oral)	Meloxicam (IM)
Tmax (hours)	1.4^x ± 0.4	3.7^y ± 0.4	1.5^x ± 0.5
Cmax (ng/mL)	333.1^x ± 94.8	327.8^x ± 94.8	5362.8^y ± 94.8
T½ (hours)	18.6^x ± 1.4	18.2^x ± 1.4	17.0^x ± 1.4
AUC (µg/mL*hours)	7.6^x ± 5.0	9.4^x ± 5.0	127.2^y ± 5.0
CL (mL/hour/kg)	144.2^x ± 10.0	120.1^x ± 10.0	8.3^y ± 10.0
MRT (hours)	25.2 ± 1.8	25.2 ± 1.8	23.9 ± 1.8
Vd (L/kg)	3.7^x ± 0.2	2.8^y ± 0.2	0.2^z ± 0.2

^a Least square mean for drugs, with different superscripts within each parameter, differed significantly (Bonferroni-corrected p < 0.01).

AUC = area under the plasma drug concentration curve; C_max, = maximum plasma concentration; CL = plasma clearance; MRT = mean residence time; T_{1/2 el} = terminal half-life; T_max = time to maximum plasma concentration; V_d = volume of distribution.

Figure 3. Least square mean (±SE) plasma concentrations of urea (a) and creatinine (b) after administration of IM firocoxib (solid black line; 1 mg/kg), oral firocoxib (dotted black line; 1 mg/kg), IM meloxicam (solid grey line; 1 mg/kg), saline (black dashdot line) to lambs (n = 15 lambs per group) that were castrated and docked on Day 0 or that were neither castrated nor docked (sham, n = 15; grey dashdot line). Mean urea and creatinine concentrations in plasma after tail docking and castration differed (Bonferroni-corrected p < 0.05) from baseline values in the meloxicam group.

Figure 4. Least square mean (±SE) average daily gain (ADG) in body weight during different time-periods in groups of lambs (n = 15 per group) that were treated with an analgesic drug (firocoxib IM:

, firocoxib oral:

, meloxicam IM:

) or and saline (oral:

) and then docked and castrated, or not (sham:

). ADG in the meloxicam IM group during 0–2 weeks following castration and docking was (Bonferroni-corrected p < 0.05) lower than the other groups. There were no between-group differences in ADG during 2–4 weeks or 4–8 weeks or overall period (0–8 weeks).