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The pharmacokinetics of cytarabine administered at three distinct subcutaneous dosing protocols in dogs with meningoencephalomyelitis of unknown origin.
Journal of Veterinary Pharmacology and Therapeutics ( IF 1.3 ) Pub Date : 2019-09-06 , DOI: 10.1111/jvp.12809
Aslynn Jones 1 , Stephanie McGrath 1 , Daniel L Gustafson 1
Affiliation  

The objective of this study was to evaluate the pharmacokinetics of the standard cytarabine (Ara-C) protocol (50 mg/m2 subcutaneously every 12 hr for 2 days) used for dogs with neuroinflammatory disease and compare it to two more practical protocols (a single 200 mg/m2 subcutaneous dose and two 100 mg/m2 subcutaneous doses every 12 hr). Four client-owned dogs previously diagnosed with meningoencephalomyelitis of unknown origin were administered three distinct Ara-C protocols with a 21-day washout between each protocol. A complete blood count was performed seven days after each dosing protocol to assess for clinically relevant myelosuppression. No adverse events were observed. Plasma Ara-C concentrations were measured using a validated liquid chromatography coupled to tandem mass spectrometry assay. The mean maximal concentrations in this study were 4,230, 9,293, and 16,675 ng/ml for a single dose of 50, 100, and 200 mg/m2 , respectively. There was a linear relationship between dose and drug exposure. Drug exposure was similar regardless of the dosing protocol when the total dose was analyzed, with an area under the concentration versus time curve of 37,026, 38,465, and 32,510 ng × hr/ml for 50, 100, and 200 mg/m2 , respectively.

中文翻译:

在未知来源的脑膜脑脊髓炎犬中,以三种不同的皮下给药方案给予阿糖胞苷的药代动力学。

这项研究的目的是评估用于患有神经炎性疾病的狗的标准阿糖胞苷(Ara-C)方案(每12小时皮下注射50 mg / m2,持续2天)的药代动力学,并将其与两种更实用的方案进行比较(单个皮下注射200毫克/平方米,每12小时两次皮下注射100毫克/平方米。对四只先前拥有未知来源的脑膜脑脊髓炎的客户拥有的狗进行三种不同的Ara-C方案治疗,每种方案之间需要21天的冲洗时间。每次给药方案后7天进行全血细胞计数,以评估临床上相关的骨髓抑制。没有观察到不良事件。使用经过验证的液相色谱和串联质谱分析法测量血浆Ara-C浓度。在这项研究中,单剂量分别为50、100和200 mg / m2时,平均最大浓度分别为4,230、9293和16675 ng / ml。剂量和药物暴露之间存在线性关系。在分析总剂量时,无论给药方案如何,药物暴露均相似,浓度,时间曲线下的面积分别为50、100和200 mg / m2,分别为37,026、38,465和32,510 ng×hr / ml。
更新日期:2019-11-01
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