牛单次皮下或静脉注射克洛苏龙后的血浆药代动力学。

IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY
Steffen Rehbein, Valerie Kvaternick, Michael Kellermann, Dietmar Hamel, Andrea Antretter, Christopher Johnson
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引用次数: 0

摘要

苯二磺酰胺衍生物clorsulon是一种强效的筋膜炎剂,以固定组合注射剂的形式上市,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,在32头健康、年轻的棕色瑞士牛中,以3 mg/kg体重或皮下注射3、6或12 mg/kg体重(每次治疗4只完整雄性和4只雌性动物),作为30%w/v克洛苏隆注射制剂。采集了多达24份的连续血液样本 给药后几天,以确定克洛苏龙的药代动力学、生物利用度和剂量比例。在第3天单次静脉注射克洛苏龙后 mg/kg体重,从给药开始到最后一次可量化浓度(AUClast)的浓度-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的反推断浓度为38500 ± 6070 ng/mL。稳态和间隙下的分布体积为685 ± 107 mL/kg和664 ± 127 mL/天/kg。在3、6或12剂量组中 通过皮下注射达到mg/kg体重,克洛苏隆的血浆浓度在0.5以内达到最大值 天,并减少到最后一个采样点。对于这些组,克洛苏隆的最大血浆浓度为3100 ± 8385250 ± 1220和10800 ± 1730 ng/mL,AUClast为5330 ± 9259630 ± 1300和21500 ± 3320 天*ng/mL。半衰期,2.01 ± 0.62、3.84 ± 1.42和5.36 ± 0.60 天,分别随着剂量的增加而显著增加,可能与剂量体积的增加有关。Clorsulon在皮下注射后被很好地吸收并完全生物利用(103%-114%)。未观察到系统暴露的性别差异。Cmax和AUClast的评估表明,在3-12的范围内,克洛苏隆皮下剂量的全身暴露量成比例增加 mg/kg体重。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Plasma pharmacokinetics of clorsulon following administration of a single subcutaneous or intravenous injection to cattle

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 (AUClast) 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 AUClast 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 Cmax and AUClast demonstrated a proportional increase in systemic exposure to the clorsulon subcutaneous doses over the range of 3–12 mg/kg body weight.

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来源期刊
CiteScore
3.10
自引率
15.40%
发文量
69
审稿时长
8-16 weeks
期刊介绍: The Journal of Veterinary Pharmacology and Therapeutics (JVPT) is an international journal devoted to the publication of scientific papers in the basic and clinical aspects of veterinary pharmacology and toxicology, whether the study is in vitro, in vivo, ex vivo or in silico. The Journal is a forum for recent scientific information and developments in the discipline of veterinary pharmacology, including toxicology and therapeutics. Studies that are entirely in vitro will not be considered within the scope of JVPT unless the study has direct relevance to the use of the drug (including toxicants and feed additives) in veterinary species, or that it can be clearly demonstrated that a similar outcome would be expected in vivo. These studies should consider approved or widely used veterinary drugs and/or drugs with broad applicability to veterinary species.
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