Cytosine arabinoside (CA) is a commonly used treatment for dogs with meningoencephalomyelitis of unknown aetiology (MUE) with various proposed protocols, many requiring 24 hours (h) of hospitalization or two visits within 24 h. This is a unidirectional study evaluating the pharmacokinetics of a CA subcutaneous (SC) protocol and a standard constant rate infusion (CRI) protocol in 8 dogs with MUE. Dogs received the CRI (200 mg/m² IV over 24 h), followed by a SC protocol (50 mg/m² every 2 h for 4 treatments) four weeks later. Plasma CA concentrations were measured by high-pressure liquid chromatography–tandem mass spectrometry (HPLC-MS). Median peak CA concentration for the SC protocol (3.40 µg/ml, range 1.60–9.70 µg/ml) was significantly higher than the CRI (1.09 µg/ml, range 0.77–1.67 µg/ml; p = .02). Median concentration at 1h and 8h following initiation of treatment was significantly higher for the SC protocol (CA₁ 2.28 µg/ml, range 0.97–2.67; CA₈ 1.83 µg/ml, range 0.77–2.84) compared to the CRI (CA1 0.01 µg/ml, range 0–0.45; CA₈ 0.74 µg/ml, range 0.67–1.11; p = .01). While the PK properties of CA when administered as a CRI has been previously investigated, this study demonstrated that CA when administered via repeated 50 mg/m² injections every 2 h over an 8-h period, provided sustained plasma levels above its therapeutic target and for a significantly longer duration of time than did a standard CRI protocol.

中文翻译：

---

胞嘧啶阿拉伯糖苷皮下注射方案对不明原因脑膜脑脊髓炎犬的药代动力学

胞嘧啶阿拉伯糖苷 (CA) 是一种常用的治疗方法，用于治疗病因不明的脑膜脑脊髓炎 (MUE) 的狗，有各种提议的方案，许多需要住院 24 小时 (h) 或在 24 小时内就诊两次。这是一项单向研究，在 8 只患有 MUE 的狗中评估 CA 皮下 (SC) 协议和标准恒速输注 (CRI) 协议的药代动力学。狗接受了 CRI（24 小时内200 mg/m ² IV），然后是 SC 协议（50 mg/m ²每 2 小时 4 次治疗）4 周后。血浆 CA 浓度通过高压液相色谱-串联质谱法 (HPLC-MS) 测量。SC 协议的中值峰值 CA 浓度（3.40 µg/ml，范围 1.60–9.70 µg/ml）显着高于 CRI（1.09 µg/ml，范围 0.77–1.67 µg/ml；p  = .02）。与 CRI (CA1 0.01 µg) 相比，SC 方案在治疗开始后 1 小时和 8 小时的中位数浓度显着更高（CA ₁ 2.28 µg/ml，范围 0.97–2.67；CA ₈ 1.83 µg/ml，范围 0.77–2.84） /ml，范围 0–0.45；CA ₈ 0.74 µg/ml，范围 0.67–1.11；p = .01）。虽然之前已经研究了作为 CRI 给药时 CA 的 PK 特性，但该研究表明，在8 小时内每 2 小时重复注射50 mg/m ²注射CA 时，可提供高于其治疗目标的持续血浆水平和比标准 CRI 协议的持续时间要长得多。