Jones Aslynn, McGrath Stephanie, Gustafson Daniel L
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO.
J Vet Pharmacol Ther. 2019 Nov;42(6):588-592. doi: 10.1111/jvp.12809. Epub 2019 Sep 6.
The objective of this study was to evaluate the pharmacokinetics of the standard cytarabine (Ara-C) protocol (50 mg/m 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/m subcutaneous dose and two 100 mg/m 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/m , 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/m , respectively.
本研究的目的是评估用于患有神经炎性疾病犬只的标准阿糖胞苷(Ara-C)方案(每12小时皮下注射50mg/m²,持续2天)的药代动力学,并将其与另外两种更实用的方案(单次皮下注射200mg/m²剂量以及每12小时皮下注射两次100mg/m²剂量)进行比较。对四只先前被诊断为不明原因脑膜脑脊髓炎的客户拥有的犬只,给予三种不同的Ara-C方案,每种方案之间间隔21天的洗脱期。在每个给药方案后7天进行全血细胞计数,以评估临床相关的骨髓抑制情况。未观察到不良事件。使用经过验证的液相色谱-串联质谱分析法测量血浆阿糖胞苷浓度。在本研究中,单次剂量50、100和200mg/m²时的平均最大浓度分别为4230、9293和16675ng/ml。剂量与药物暴露之间存在线性关系。当分析总剂量时,无论给药方案如何,药物暴露情况相似,50、100和200mg/m²时浓度-时间曲线下面积分别为37026、38465和32510ng×hr/ml。