Pharmacokinetics, Activity, and Residue Elimination of R- and S-Diclazuril in Broiler Chickens.

Abstract

Diclazuril (DIC) is widely used as a racemic mixture to prevent and treat coccidiosis in farm animals, while the pharmacokinetics, bioactivity, and toxicity of DIC enantiomers are not known at all. This study first established a simple, sensitive, and reliable liquid chromatography tandem mass spectrometry method for separation of R-DIC and S-DIC and their analyses. Then, it was applied to investigate the stereoselective pharmacokinetics and residual elimination of individual enantiomers, and their anticoccidial activity was also evaluated in broiler chickens. The results indicated that the area under the concentration-time curve (AUC) and elimination half-life (t1/2β) were significantly different (p < 0.05) for two enantiomers in chicken plasma. The AUC and t1/2β of S-DIC were approximately 2 and 1.4 times those of R-DIC, respectively. The residual elimination of DIC enantiomers in chicken tissues was also stereoselective. The concentrations of S-DIC in chicken muscle and liver were greater than those of R-DIC, and it is the opposite in the kidney. There was no significant difference (p > 0.05) in the anticoccidial activity of racemate and enantiomers when a single enantiomer in feed was added above 0.5 mg kg-1. However, the anticoccidial activity of R-DIC (0.25 mg kg-1) was significantly higher (p < 0.05) than that of S-DIC (0.25 mg kg-1) in the diet. It should be mentioned that in chicken small intestine and cecum, the enantiomerization rate of each enantiomer in the infection group was faster than that in the uninfected group.

• Authors: Meiyu Zhang, Jingli Qiu, Xiaogui Shu, Xiaoling Tang, Xuefang Sha, Li Wu, Jun Fan, Dongping Zeng, Rujian He, Weiguang Zhang, Zhenling Zeng, Rong Liu, Limin He
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 68 Issue 33 Pg. 8987-8995 (Aug 19 2020) ISSN: 1520-5118 [Electronic] United States
• PMID: 32692165 (Publication Type: Journal Article)

Chemical References

• Coccidiostats
• Nitriles
• Triazines
• diclazuril

Topics

• Animals
• Chickens (blood)
• Coccidiostats (blood, chemistry, pharmacology)
• Drug Residues (chemistry, pharmacokinetics)
• Nitriles (blood, chemistry, pharmacokinetics)
• Stereoisomerism
• Triazines (blood, chemistry, pharmacokinetics)