Pharmacokinetics of toltrazuril and its metabolites toltrazuril sulphoxide and toltrazuril sulphone in pregnant and non-pregnant goats

Elazab, Sara T.; Elshater, Nahla S.; Elweza, Ahmed E.

doi:10.2754/avb202190040383

Acta Veterinaria > Archive > 2021, Vol. 90 > Issue 4 > Pharmacokinetics of toltrazuril and its…

Acta Vet. Brno 2021, 90: 383-390

https://doi.org/10.2754/avb202190040383

Pharmacokinetics of toltrazuril and its metabolites toltrazuril sulphoxide and toltrazuril sulphone in pregnant and non-pregnant goats

Sara T. Elazab¹, Nahla S. Elshater², Ahmed E. Elweza³

¹Mansoura University, Faculty of Veterinary Medicine, Department of Pharmacology, Mansoura, Egypt
²Agriculture Research Center, Animal Health Research Institute, Giza-Dokki, Egypt
³University of Sadat City, Faculty of Veterinary Medicine, Department of Theriogenology, Sadat City, Menoufia, Egypt

Received August 9, 2021
Accepted November 9, 2021

The pharmacokinetic characteristics of toltrazuril (TZR) and its metabolites toltrazuril sulphoxide (TZR.SO) and toltrazuril sulphone (TZR.SO₂) were assessed in non-pregnant and pregnant goats. Ten healthy Baladi female goats were allocated into two groups (n = 5 per group): non-pregnant goats (group 1) and pregnant goats at 2–3 months of gestation (group 2). Toltrazuril was administered once orally to all goats at 20 mg/kg. Plasma samples were collected at 0 (before TZR administration), 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72 h and 5, 7, 9, 12, 16, 20, 24, 27, 30, and 35 days post therapy to measure the concentrations of TZR and its metabolites. In pregnant goats, the maximum plasma concentration (C_max), time to reach C_max (T_max), and the area under the plasma concentration-time curve from time zero to the last sample (AUC_0-last) of TZR were significantly higher (P < 0.05) compared to the non-pregnant ones, whereas the volume of distribution (Vz_F_obs) and clearance (Cl_F_obs) were significantly lower (P < 0.05) in pregnant goats. No significant differences were observed in the elimination half-life (T_1/2λz), and mean residence time (MRT) between the two groups. In non-pregnant goats, TZR.SO and TZR.SO₂ could be detected in plasma until 12 and 30 days, respectively; whereas in pregnant goats, they were quantified up to 16 and 35 days, respectively. Conclusively, TZR was well absorbed and rapidly metabolized to TZR.SO and TZR.SO₂, after oral dosing in goats. Pregnancy caused significant alterations in some of the pharmacokinetic indicators of TZR and its metabolites in goats.

Keywords

Triazines, toxoplasmosis, elimination half-life, volume of distribution, HPLC.

Funding

We would like to thank the staff members of Animal Health Research institute Giza-Dokki, Egypt for their help in measuring the concentration of toltrazuril in plasma samples using HPLC. Also, we appreciate the assistance of of Mr. Ahmed Abbas with the animal experiment. We thank Mrs. Rawia Abu El-Atta, a Master degree holder in English Literature, Al-Azhar University, Cairo for the English editing.