Exploring flubendazole formulations for use in sheep. Pharmacokinetic evaluation of a cyclodextrin-based solution

BMC Veterinary Research

Table 2 Plasma pharmacokinetic parameters (mean ± SD) for flubendazole (FLBZ) and its reduced metabolite (R-FLBZ), obtained after the intraruminal (i.r.) administration of FLBZ (3.8 mg/kg, n = 6) formulated as a cyclodextrin-based solution (FLBZ-CDs) or a carboximethylcelullose suspension (FLBZ-CMC) to sheep (Experiment 1)

PHARMACOKINETIC PARAMETERS	FLBZ			R-FLBZ
PHARMACOKINETIC PARAMETERS	FLBZ-CDs⁽¹⁾i.r. treatment	FLBZ-CMC⁽¹⁾i.r. treatment	FLBZ-CDs⁽²⁾i.a. treatment	FLBZ-CDs⁽¹⁾i.r. treatment	FLBZ-CMC⁽¹⁾i.r. treatment	FLBZ-CDs⁽²⁾i.a. treatment
T½abs/for (h)	3.67 ± 1.57	2.92 ± 0.94	0.40 ± 1.43*	3.00 ±1.21	4.95 ± 1.72	0.90 ± 0.30*
Cmax (μg/mL)	0.05 ± 0.01	0.03 ± 0.01	0.07 ± 0.04*	0.23 ± 0.04	0.14 ± 0.03*	0.35 ± 0.09*
Tmax (h)	12.0 ± 3.79	12.5 ± 2.95	2.75 ± 2.36*	10.5 ± 4.93	11.5 ± 1.22	2.75 ± 1.50*
AUC_0-t (μg.h/mL)	1.35 ± 0.34	0.78 ± 0.53	0.65 ± 0.29	6.82 ± 1.77	4.92 ± 1.46	3.83 ± 1.86*
T½el (h)	25.8 ± 14.0	19.2 ± 15.1	15.1 ± 8.27*	17.0 ± 5.19	18.4 ± 3.74	6.73 ± 3.70*
MRT (h)	41.6 ± 19.0	34.5 ± 20.3	19.7 ± 9.73*	28.8 ± 8.58	35.4 ± 3.90	10.8 ± 4.07*

The pharmacokinetic parameters obtained after the intra-abomasal (i.a.) administration of FLBZ (3.8 mg/kg, n = 4) formulated as a cyclodextrin-based solution (FLBZ-CDs), is also shown (Experiment 2). T½abs/for: FLBZ absorption or metabolite formation half life; Cmax: peak plasma concentration; Tmax: time to the Cmax; AUC_0-t: Area under the plasma concentration vs. time curve from 0 to the detection time; T½el: elimination half-life; MRT: mean residence time (obtained by non-compartmental analysis of the data). *Significantly different from the FLBZ-CDs i.r. treated group at P < 0.05.
¹Experiment 1: crossover design (n = 6) sheep were treated with the HPβCD-FLBZ solution (FLBZ-CDs) or the CMC-FLBZ suspension (FLBZ-CMC) by the i.r. route at the same dose rate (3.8 mg/kg).
²Experiment 2: intraabomasal (i.a.) administration of the FLBZ-CDs solution (3.8 mg/kg, n = 4).

ISSN: 1746-6148