The benzenedisulfonamide derivative clorsulon is a potent fasciolicide which is marketed in fixed combination injectables, typically combined with the macrocyclic lactone ivermectin. In the presented pharmacokinetic study, the plasma profile of clorsulon in 32 healthy, young Brown Swiss cattle was administered a single intravenous dose at 3 mg/kg body weight or subcutaneously at 3, 6 or 12 mg/kg body weight (4 intact male and 4 female animals per treatment) as a 30% w/v clorsulon injection formulation. Serial blood samples were collected up to 24 days after administration to establish the pharmacokinetics, bioavailability and dose proportionality of clorsulon. Following a single intravenous injection of clorsulon at 3 mg/kg body weight, the area under the concentration versus time curve from the start of dose administration to the time of the last quantifiable concentration (AUC_last) was 4830 ± 941 day*ng/mL, and half-live was 2.37 ± 0.98 days. The back extrapolated concentration at time 0 was 38,500 ± 6070 ng/mL. The volume of distribution at steady state and clearance were 685 ± 107 mL/kg and 664 ± 127 mL/day/kg, respectively. In the groups dosed at 3, 6 or 12 mg/kg body weight by subcutaneous injection, clorsulon plasma concentrations rose to maximum within 0.5 day and decreased to the last sample point. For these groups, the maximum plasma clorsulon concentrations were 3100 ± 838, 5250 ± 1220 and 10,800 ± 1730 ng/mL, respectively, and the AUC_last was 5330 ± 925, 9630 ± 1300 and 21,500 ± 3320 day*ng/mL, respectively. Half-lives, 2.01 ± 0.62, 3.84 ± 1.42 and 5.36 ± 0.60 days, respectively, increased significantly with dose, likely related to increasing dose volume. Clorsulon was well absorbed and fully bioavailable (103%–114%) after subcutaneous injection. No gender-related difference in systemic exposure was observed. Assessment of C_max and AUC_last demonstrated a proportional increase in systemic exposure to the clorsulon subcutaneous doses over the range of 3–12 mg/kg body weight.

中文翻译：

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牛单次皮下或静脉注射后氯磺隆的血浆药代动力学

苯二磺酰胺衍生物氯磺隆是一种强效的片形杀虫剂，以固定组合注射剂形式销售，通常与大环内酯伊维菌素组合。在所提出的药代动力学研究中，对 32 头健康年轻棕色瑞士牛进行了单次静脉注射剂量 3 mg/kg 体重或皮下注射剂量 3、6 或 12 mg/kg 体重（4 只完整雄性和每次治疗 4 只雌性动物）作为 30% w/v 氯舒隆注射制剂。给药后 24 天收集连续血样，以确定氯舒隆的药代动力学、生物利用度和剂量比例。以 3 mg/kg 体重单次静脉注射氯舒隆后，从给药开始到最后可定量浓度（AUC 最后_）的浓度与时间曲线下面积为 4830 ± 941 天*ng/mL ，半衰期为 2.37 ± 0.98 天。时间 0 时的反推浓度为 38,500 ± 6070 ng/mL。稳态和清除时的分布容积分别为 685 ± 107 mL/kg 和 664 ± 127 mL/天/kg。在通过皮下注射以3、6或12mg/kg体重给药的组中，氯磺隆血浆浓度在0.5天内升至最大值并下降至最后一个采样点。_{对于这些组，最大血浆氯舒隆浓度分别为 3100 ± 838、5250 ± 1220 和 10,800 ± 1730 ng/mL，最后}AUC 分别为5330 ± 925、9630 ± 1300 和 21,500 ± 3320 天*ng/mL 。半衰期分别为 2.01 ± 0.62、3.84 ± 1.42 和 5.36 ± 0.60 天，随着剂量的增加而显着增加，可能与剂量体积的增加有关。皮下注射后，氯磺隆吸收良好，生物利用度完全 (103%–114%)。没有观察到全身暴露量与性别相关的差异。C _max和 AUC的评估_最后表明，在 3-12 mg/kg 体重范围内，氯舒隆皮下剂量的全身暴露量成比例增加。