Toltrazuril

Toltrazuril is a veterinary drug coccidiostatic. Toltrazuril (TZR), 1-methyl-3- [3-methyl] -4 [4- (trifluoromethylsulfanyl) phenoxy] phenyl] -1, 3,5-triazinane-2,4,6-trione is a symmetric triazinetrione compound. It has a coccidicidal effect at all intracellular stages of development, including schizogony and gametogony (Mehlhorn et al., 1984; Haberkorn and Stoltefuss, 1987). It is known to be effective against all types of coccidia in most animal species, such as chickens (Mehlhorn et al., 1984), ducks (Chauve et al., 1994), dogs (Daugschies et al., 2000), mice (Haberkorn et al., al., 1983), pigeons (Van Reeth and Vercruysse, 1993), piglets (Mundt et al., 2007) and rabbits (Peeters and Geeroms, 1986). TZR undergoes extensive metabolism to toltrazuril sulfate (TZR-SO) and then to TZR-SO2, which appears to have anti-coccidial activity (Benoit et al., 1993; Lang et al., 1996; Bach et al., 2003; Mundt et al., 2007). In general, triazines produce the same types of metabolites in most species, but the ratios of metabolites showed a number of differences (Ferr and Kennedy, 2000; McKay, 2006; Kim et al., 2010; Lim et al., 2010). In addition, TZR is almost exclusively metabolized to TZR-SO2, also known as ponazuril (PZR), which has been recognized as a metabolite marker in a number of tissues. Although TZR is commonly used to prevent and treat coccidosis in broilers, the pharmacokinetic and metabolic profiles of TZR in broilers have received minimal research. In general, coccidiostatics are used to combat coccidiosis, a disease caused by coccidia, a single-celled parasite of the genus Eimeria. They are mainly used in nutritional supplements for fattening chickens, for treatment and prevention on farms, where diseases are more common due to high humidity, high temperatures or dirt. Toltrazuril is a synthetic derivative of triazinetrione that is used as an oral suspension in drinking water for the treatment of coccidiosis in chickens, turkeys, pigs and cattle. The recommended dose and duration of treatment for chickens and turkeys is 7 mg / kg body weight per day for two consecutive days. Pharmacological studies have shown that toltrazuril is well absorbed in the gastrointestinal tract and is rapidly metabolized to toltrazuril sulfoxide and toltrazuril sulfone, also known as ponazuril. Toltrazuril sulfone is slowly cleared from the tissues of chickens, turkeys and calves and is considered a marker for toltrazuril residues. For example, the residues of toltrazuril sulfone in calves after administration of a single oral dose of toltrazuril 15 mg / kg body weight can be determined 42 days after administration with concentrations (μg / kg): 848 in liver, 393 in kidney, 99 in muscle and 260 in adipose tissue. … In addition, toltrazuryl sulfone residues can still be detected in liver samples 70 days after treatment. Toxicological studies of toltrazuril in rats have shown that higher doses cause significant weight loss, changes in blood counts and abnormal liver function, as well as teratogenic and embryotoxic effects such as long bone dysplasia and a significant decrease in fetal numbers.