The objectives of this study were to determine the pharmacokinetics of toltrazuril and its metabolites in pregnant and nonpregnant ewes following a single oral dose and to determine the plasma concentrations of these compounds in milk, allantoic fluid, and newborn plasma. Eighteen healthy ewes were randomly divided into three groups (n  = 6 each): pregnant ewes at 12–13 weeks of gestation (group A), nonpregnant ewes (group B), and pregnant ewes at 1–2 weeks before expected lambing date (group C). Ewes in all groups received a single oral dose of toltrazuril at 20 mg/kg body weight. In groups A and B, blood samples were collected at 1, 3, 5, 7, 9, 12, 15, 18 hr, every 6 hr to day 3, every 12 hr to day 7 and thereafter every 24 hr to day 14 post‐toltrazuril administration. In group C, parturition was induced 24–36 hr after toltrazuril administration then milk, allantoic fluid, and newborn plasma samples were collected immediately after birth. Drug metabolites were assayed using ultra high‐performance liquid chromatography–ultraviolet detection method (UHPLC‐UV). The maximum concentration (C_max), area under the plasma concentration‐time curve (AUC_0–t), AUC to 24 and 48 hr (AUC_0–24), and (AUC_0–48) were significantly higher in pregnant ewes. Longer apparent half‐life (T_1/2), significantly higher apparent volume of distribution (Vd/F) and total clearance (Cl/F) were observed in nonpregnant ewes. The time to maximum plasma concentration (T_max), mean residence time (MRT) and elimination rate constant (K_el) were similar in both groups. The AUC_0–24 and AUC_0–48 were significantly higher in nonpregnant ewes. The AUC_0–t was significantly higher in pregnant ones. The ratio of plasma toltrazuril concentrations in ewes and toltrazuril concentrations in newborn lambs' plasma, allantoic fluid, and milk were 68%, 2.3%, and 5.3%, respectively. Results of this study showed that toltrazuril is well absorbed after a single oral dose in ewes with widespread distribution in different body tissues.

中文翻译：

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托特扎脲及其代谢产物在孕妇和非孕妇母羊中的药代动力学，并测定其在牛奶，尿囊液和新生儿血浆中的浓度。

这项研究的目的是确定单次口服剂量后托拉祖利及其代谢产物在孕妇和未怀孕母羊中的药代动力学，并确定牛奶，尿囊液和新生儿血浆中这些化合物的血浆浓度。将18头健康母羊随机分为三组（n 每只= 6）：妊娠12-13周的母羊（A组），未怀孕的母羊（B组）和预期的产羔日期前1-2周的母羊（C组）。所有组的母羊均接受口服口服托他祖利的剂量为20 mg / kg体重。在A组和B组中，在术后第1、3、5、7、9、12、15、18小时，每6小时至第3天，每12小时至第7天以及此后每24小时至第14天收集血液样本盐酸托曲唑的给药。在C组中，在给予托曲脲治疗后24-36小时引起分娩，然后在出生后立即收集牛奶，尿囊液和新生儿血浆样品。使用超高效液相色谱-紫外线检测方法（UHPLC-UV）测定药物代谢产物。最大浓度（C _max）时，血浆浓度-时间曲线（AUC下面积_0-T），AUC 24和48小时（AUC _0-24）和（AUC _0-48）在怀孕母羊均显著高。在未怀孕的母羊中观察到更长的表观半衰期（T _1/2），表观分布体积（Vd / F）和总清除率（Cl / F）。两组达到最大血浆浓度的时间（T _max），平均停留时间（MRT）和消除速率常数（K _el）相似。非妊娠母羊的AUC _0-24和AUC _0-48显着更高。AUC _0–t在孕妇中明显更高。母羊血浆中托拉西里的血浆浓度与新生羔羊血浆，尿囊液和牛奶中的托拉西利浓度的比例分别为68％，2.3％和5.3％。这项研究的结果表明，单次口服剂量的母羊中的托特沙脲可被良好吸收，并分布在不同的身体组织中。