Toltrazuril sulfone
(Synonyms: 妥曲珠利砜; Ponazuril) 目录号 : GC37813
An active metabolite of toltrazuril
Cas No.:69004-04-2
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Toltrazuril sulfone is an active metabolite of the coccidiostat toltrazuril .1 Toltrazuril sulfone is formed from toltrazuril via the intermediate metabolite toltrazuril sulfoxide by cytochrome P450 (CYP) enzymes, including CYP3A. It inhibits T. gondii tachyzoite production in African green monkey kidney cells when used at concentrations of 0.1, 1, and 5 ?g/ml.2 Toltrazuril sulfone completely prevents infection with T. gondii tachyzoites in a mouse model of fatal toxoplasmosis when administered at doses of 10 or 20 mg/kg one day prior to, and daily for 10 days following, infection. It also reduces the number of infected mice in the same model when administered at a dose of 10 mg/kg for 11 days starting six days following infection. Formulations containing toltrazuril sulfone have been used in the treatment of equine protozoal myeloencephalitis (EPM) in horses.
1.Benoit, E., Buronfosse, T., Moroni, P., et al.Stereoselective S-oxygenation of an aryl-trifluoromethyl sulfoxide to the corresponding sulfone by rat liver cytochromes P450Biochem. Pharmacol.46(12)2337-2341(1993) 2.Mitchell, S.M., Zajac, A.M., Davis, W.L., et al.Efficacy of ponazuril in vitro and in preventing and treating Toxoplasma gondii infections in miceJ. Parasitol.90(3)639-642(2004)
| Cas No. | 69004-04-2 | SDF | |
| 别名 | 妥曲珠利砜; Ponazuril | ||
| Canonical SMILES | O=S(C1=CC=C(C=C1)OC2=C(C=C(C=C2)N3C(N(C(NC3=O)=O)C)=O)C)(C(F)(F)F)=O | ||
| 分子式 | C18H14F3N3O6S | 分子量 | 457.38 |
| 溶解度 | DMSO: ≥ 33 mg/mL (72.15 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.1864 mL | 10.9318 mL | 21.8637 mL |
| 5 mM | 0.4373 mL | 2.1864 mL | 4.3727 mL |
| 10 mM | 0.2186 mL | 1.0932 mL | 2.1864 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Toltrazuril sulfone sodium salt: synthesis, analytical detection, and pharmacokinetics in the horse
J Vet Pharmacol Ther 2012 Jun;35(3):265-74.PMID:21679197DOI:10.1111/j.1365-2885.2011.01315.x.
Toltrazuril sulfone (ponazuril) is a triazine-based antiprotozoal agent with clinical application in the treatment of equine protozoal myeloencephalomyelitis (EPM). In this study, we synthesized and determined the bioavailability of a sodium salt formulation of Toltrazuril sulfone that can be used for the treatment and prophylaxis of EPM in horses. Toltrazuril sulfone sodium salt was rapidly absorbed, with a mean peak plasma concentration of 2400 ± 169 (SEM) ng/mL occurring at 8 h after oral-mucosal dosing and was about 56% bioavailable compared with the i.v. administration of Toltrazuril sulfone in dimethylsulfoxide (DMSO). The relative bioavailability of Toltrazuril sulfone suspended in water compared with Toltrazuril sulfone sodium salt was 46%, indicating approximately 54% less oral bioavailability of this compound suspended in water. In this study, we also investigated whether this salt formulation of Toltrazuril sulfone can be used as a feed additive formulation without significant reduction in oral bioavailability. Our results indicated that Toltrazuril sulfone sodium salt is relatively well absorbed when administered with feed with a mean oral bioavailability of 52%. Based on these data, repeated oral administration of Toltrazuril sulfone sodium salt with or without feed will yield effective plasma and cerebrospinal fluid (CSF) concentrations of Toltrazuril sulfone for the treatment and prophylaxis of EPM and other protozoal diseases of horses and other species. As such, Toltrazuril sulfone sodium salt has the potential to be used as feed additive formulations for both the treatment and prophylaxis of EPM and various other apicomplexan diseases.
Risk of residues of Toltrazuril sulfone in eggs after oral administration - Could setting maximum residue limit be helpful?
Food Chem 2021 Oct 30;360:130054.PMID:34020367DOI:10.1016/j.foodchem.2021.130054.
A depletion study of toltrazuril and its metabolites was performed using 20 hens medicated via drinking water for two days in a dosage of 7 mg kg-1 per kg body weight. Afterward, eggs were collected for 42 days. Residues were analyzed in whole eggs and yolk and whites. Toltrazuril sulfone was found to be the most predominant in all matrices, the highest concentration was found in the yolk - 5567 µg kg-1, followed by whole eggs samples - 4767 µg kg-1 and egg whites - 532 µg kg-1. On last day Toltrazuril sulfone were still detected - 22.5 µg kg-1. 70 days is required to concentration of Toltrazuril sulfone reach zero. Administrating toltrazuril before the laying phase can pose a risk of residues of Toltrazuril sulfone in eggs. Setting Maximum Residue Limit could reduce the risk of non-complaint samples and ensure the safety of consumers, but still requires 44 days of the withdrawal period.
Detection, quantifications and pharmacokinetics of Toltrazuril sulfone (Ponazuril) in cattle
J Vet Pharmacol Ther 2009 Jun;32(3):280-8.PMID:19646093DOI:10.1111/j.1365-2885.2008.01039.x.
Toltrazuril sulfone (Ponazuril) is a triazine-based anti-protozoal agent with highly specific actions against apicomplexan group of organisms, which are undergoing intensive investigation. Toltrazuril sulfone may have clinical application in the treatment of Neospora. caninum and other protozoal infections in cattle. To evaluate absorption, distribution, and elimination characteristics of Toltrazuril sulfone in cattle, a sensitive validated quantitative high-pressure liquid chromatography method for Toltrazuril sulfone in bovine biological fluids was developed. After a single oral dose of Toltrazuril sulfone at 5 mg/kg (as 150 mg/g of Marquis; Bayer HealthCare, Shawnee Mission, KS, USA), samples from six cows showed good plasma concentrations of Toltrazuril sulfone, which peaked at 4821 ng/mL +/- 916 (SD) at 48 h postadministration. Thereafter, plasma concentration declined to 1950 ng/mL +/- 184 (SD) at 192 h after administration with an average plasma elimination half-life of approximately 58 h. Following oral dose of Toltrazuril sulfone, the observed peak plasma concentrations were in relatively close agreement ranging from the lowest 3925 ng/mL to the highest of 6285 ng/mL with the mean peak plasma concentration being 4821 ng/mL. This study shows that Toltrazuril sulfone is relatively well absorbed after oral dose in cattle. These results are therefore entirely consistent with and support the reported clinical efficacy of Toltrazuril sulfone in the treatment of experimentally induced clinical cases of N. caninum and other protozoal-mediated bovine diseases.
Plasma disposition of toltrazuril and its metabolites, toltrazuril sulfoxide and Toltrazuril sulfone, in rabbits after oral administration
Vet Parasitol 2010 Apr 19;169(1-2):51-6.PMID:20083354DOI:10.1016/j.vetpar.2009.12.011.
The objective of this study was to evaluate the pharmacokinetic profiles of toltrazuril (TZR), and its major metabolites toltrazuril sulfoxide (TZR x SO) and Toltrazuril sulfone (TZR x SO(2)) in rabbits after oral administrations. Rabbits were dosed once with 10 and 20mg/kg TZR via stomach tube with manual restraint. The plasma concentrations of TZR, TZR x SO and TZR x SO(2) were determined by liquid chromatography/mass spectrometry. Plasma concentration-time data after single oral administration were analyzed by a non-compartmental analysis. Plasma peak concentrations of TZR, TZR x SO and TZR x SO(2) were 30.2+/-1.5microg/mL at 20.0+/-6.9h, 8.9+/-1.3microg/mL at 20.0+/-6.9h and 14.7+/-3.9microg/mL at 96.0+/-0.0h after oral administration of TZR with 10mg/kg bw, respectively. The terminal elimination half-lives for TZR, TZR x SO and TZR x SO(2) after oral dose of 10mg/kg were 52.7+/-3.6, 56.1+/-10.7 and 76.7+/-7.5h, respectively. Plasma peak concentrations of TZR, TZR x SO and TZR x SO(2) were 39.4+/-1.2microg/mL at 28.0+/-6.9h, 12.5+/-3.9microg/mL at 20.0+/-6.9h and 24.9+/-8.74microg/mL at 112.0+/-6.9h after oral administration of TZR with 20mg/kg bw, respectively. The terminal elimination half-lives for TZR, TZR x SO and TZR x SO(2) after oral dose of 20mg/kg were 56.7+/-1.9, 68.8+/-12.5 and 82.3+/-12.6h, respectively. In conclusion, TZR was very well-absorbed through the gastrointestinal tract and rapidly metabolized to TZR x SO and TZR x SO(2) in rabbits after oral administration. TZR x SO(2) was actually more slowly eliminated than TZR and TZR x SO.
Absorption and Distribution of Toltrazuril and Toltrazuril sulfone in Plasma, Intestinal Tissues and Content of Piglets after Oral or Intramuscular Administration
Molecules 2021 Sep 16;26(18):5633.PMID:34577103DOI:10.3390/molecules26185633.
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.