Pharmacokinetics of a novel triazine ethanamizuril in rats and broiler chickens

Cheng, Peipei; Wang, Chunmei; Lin, Xi; Zhang, Lifang; Fei, Chenzhong; Zhang, Keyu; Zhao, Juan; Lei, Na; Liu, Huan; Mu, Shuhua; Wang, Xiaoyang; Wang, Mi; Zheng, Wenli; Liu, Yingchun; Guo, Chunna; Xue, Feiqun

doi:10.1016/j.rvsc.2017.11.001

Cited by 12 publications

(7 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most active compound, nitromezuril, is being developed as an anticoccidial for poultry [ 29 , 30 , 31 ]. Aminomizuril and ethanamizuril, the active metabolites of nitromezuril, and acetamizuril are also new development candidates [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Absorption and Distribution of Toltrazuril and Toltrazuril Sulfone in Plasma, Intestinal Tissues and Content of Piglets after Oral or Intramuscular Administration

et al. 2021

View full text Add to dashboard Cite

Piglet coccidiosis due to Cystoisospora suis is a major cause of diarrhea and poor growth worldwide. It can effectively be controlled by application of toltrazuril (TZ), and oral formulations have been licensed for many years. Recently, the first parenteral formulation containing TZ in combination with iron (gleptoferron) was registered in the EU for the prevention of coccidiosis and iron deficiency anemia, conditions in suckling piglets requiring routine preventive measures. This study evaluated the absorption and distribution of TZ and its main metabolite, toltrazuril sulfone (TZ-SO2), in blood and intestinal tissues after single oral (20 mg/kg) or single intramuscular (45 mg/piglet) application of TZ. Fifty-six piglets were randomly allocated to the two treatment groups. Animals were sacrificed 1-, 5-, 13-, and 24-days post-treatment and TZ and TZ-SO2 levels were determined in blood, jejunal tissue, ileal tissue, and mixed jejunal and ileal content (IC) by high performance liquid chromatography (HPLC). Intramuscular application resulted in significantly higher and more sustained concentrations of both compounds in plasma, intestinal tissue, and IC. Higher concentrations after oral dosing were only observed one day after application of TZ in jejunum and IC. Toltrazuril was quickly metabolized to TZ-SO2 with maximum concentrations on day 13 for both applications. Remarkably, TZ and TZ-SO2 accumulated in the jejunum, the primary predilection site of C. suis, independently of the administration route, which is key to their antiparasitic effect.

show abstract

Section: Discussionmentioning

confidence: 99%

Absorption and Distribution of Toltrazuril and Toltrazuril Sulfone in Plasma, Intestinal Tissues and Content of Piglets after Oral or Intramuscular Administration

et al. 2021

View full text Add to dashboard Cite

show abstract

“…However, the subclinical and clinical effects of coccidiosis result in malabsorption, reduced feed conversion rate and weight gain, and an increase in mortality and susceptibility to secondary disease in infected chickens (Prakashbabu et al 2017). Consequently, the livestock industry suffers a global loss exceeding $3 billion dollars, making precautions to control the disease fundamental (Cheng et al 2018).…”

Section: Introductionmentioning

confidence: 99%

A review of Eimeria antigen identification for the development of novel anticoccidial vaccines

Venkatas

Adeleke

2019

Parasitol Res

View full text Add to dashboard Cite

Coccidiosis is a major poultry disease which compromises animal welfare and costs the global chicken industry a huge economic loss. As a result, research entailing coccidial control measures is crucial. Coccidiosis is caused by Eimeria parasites that are highly immunogenic. Consequently, a low dosage of the Eimeria parasite supplied by a vaccine will enable the host organism to develop an innate immune response towards the pathogen. The production of traditional live anticoccidial vaccines is limited by their low reproductive index and high production costs, among other factors. Recombinant vaccines overcome these limitations by eliciting undesired contaminants and prevent the reversal of toxoids back to their original toxigenic form. Recombinant vaccines are produced using defined Eimeria antigens and harmless adjuvants. Thus, studies regarding the identification of potent novel Eimeria antigens which stimulate both cell-mediated and humoral immune responses in chickens are essential. Although the prevalence and risk posed by Eimeria have been well established, there is a dearth of information on genetic and antigenic diversity within the field. Therefore, this paper discusses the potential and efficiency of recombinant vaccines as an anticoccidial control measure. Novel protective Eimeria antigens and their antigenic diversity for the production of cheap, easily accessible recombinant vaccines are also reviewed.

show abstract

“…The structure of N‐(4‐(4‐(3,5‐dioxo‐4,5‐dihydro‐1,2,4‐triazin‐2‐[3H]‐yl)‐2‐methylphenoxy) phenyl) acetamide, also known as ethanamizuril (CAS:1560840–75‐6, Figure 1), is similar to that of diclazuril and toltrazuril and has been developed independently in recent years by the Shanghai Veterinary Research Institute of the Chinese Academy of Agricultural Sciences (Cheng et al, 2018; Zhang et al, 2014; Zhao et al, 2017). Ethanamizuril exhibits remarkable anticoccidial activity when supplemented at 7–10 ppm in the tap water or 7–10 ppm in the diet on 2–3 consecutive days and only a few fecal oocysts and slight caecal lesions are observed after treatment of infected chickens.…”

Section: Introductionmentioning

confidence: 99%

Two‐generation reproduction and limited teratology studies of ethanamizuril fed to rats

Zhao

Wang

et al. 2020

Birth Defects Research

Self Cite

View full text Add to dashboard Cite

Ethanamizuril, a new anticoccidial agent that belongs to triazine derivatives, has a broad and good anticoccidial activity. To evaluate the reproductive toxicity and teratogenic potential of ethanamizuril, different concentrations of ethanamizuril were administered to Sprague-Dawley rats by feeding diets containing 0, 2, 8, and 30 ppm, respectively. Each group consisting of 30 males and 30 females (F0) was treated with different concentrations of ethanamizuril through a 13-week period before mating and during mating, gestation, parturition and lactation. In the 30 ppm dose group, pup body weight on days 7 and 21 in F1 offspring and day 21 in the F2a offspring were significantly decreased.A limited teratogenicity study was performed in combination with the F1 generation of a two-generation reproduction study. F1 offspring of the reproduction study were mated after weaning of the F2a offspring. Pregnant female rats were subjected to cesarean section on gestational day 20 for teratogenic examination. No obvious body weights, fetal body lengths, tail lengths, litter weights, number of viable fetuses, external, skeletal, or visceral malformations in fetuses were noted in any groups in the teratogenic test, but ethanamizuril could be passed on to offspring through lactation. K E Y W O R D S ethanamizuril, feeding in diet, reproductive toxicity, Sprague-Dawley rats, teratogenicity

show abstract

Pharmacokinetics of a novel triazine ethanamizuril in rats and broiler chickens

Cited by 12 publications

References 8 publications

Absorption and Distribution of Toltrazuril and Toltrazuril Sulfone in Plasma, Intestinal Tissues and Content of Piglets after Oral or Intramuscular Administration

Absorption and Distribution of Toltrazuril and Toltrazuril Sulfone in Plasma, Intestinal Tissues and Content of Piglets after Oral or Intramuscular Administration

A review of Eimeria antigen identification for the development of novel anticoccidial vaccines

Two‐generation reproduction and limited teratology studies of ethanamizuril fed to rats

Contact Info

Product

Resources

About