Veterinary Specialty Services-Neurology, Manchester, MO.
Department of Clinical Sciences, North Carolina State University Veterinary Hospital, Raleigh, NC.
Am J Vet Res. 2022 Jul 22;83(9):ajvr.22.03.0046. doi: 10.2460/ajvr.22.03.0046.
To investigate the feasibility and pharmacokinetics of cytarabine delivery as a subcutaneous continuous-rate infusion with the Omnipod system.
6 client-owned dogs diagnosed with meningoencephalomyelitis of unknown etiology were enrolled through the North Carolina State University Veterinary Hospital.
Cytarabine was delivered at a rate of 50 mg/m2/hour as an SC continuous-rate infusion over 8 hours using the Omnipod system. Plasma samples were collected at 0, 4, 6, 8, 10, 12, and 14 hours after initiation of the infusion. Plasma cytarabine concentrations were measured by high-pressure liquid chromatography. A nonlinear mixed-effects approach generated population pharmacokinetic parameter estimates.
The mean peak plasma concentration (Cmax) was 7,510 ng/mL (range, 5,040 to 9,690 ng/mL; SD, 1,912.41 ng/mL), average time to Cmax was 7 hours (range, 4 to 8 hours; SD, 1.67 hours), terminal half-life was 1.13 hours (SD, 0.29 hour), and the mean area under the curve was 52,996.82 hours X μg/mL (range, 35,963.67 to 71,848.37 hours X μg/mL; SD, 12,960.90 hours X μg/mL). Cmax concentrations for all dogs were more than 1,000 ng/mL (1.0 μg/mL) at the 4-, 6-, 8-, and 10-hour time points.
An SC continuous-rate infusion of cytarabine via the Omnipod system is feasible in dogs and was able to achieve a steady-state concentration of more than 1 μg/mL 4 to 10 hours postinitiation of cytarabine and a Cmax of 7,510 ng/mL (range, 5,040 to 9,690 ng/mL; SD, 1,912.41 ng/mL). These are comparable to values reported previously with IV continuous-rate infusion administration in healthy research Beagles and dogs with meningoencephalomyelitis of unknown etiology.
研究阿糖胞苷经皮下持续输注方式给予奥姆尼泊德系统的可行性和药代动力学。
6 只经临床诊断为病因不明的脑膜脑脊髓炎的患犬，通过北卡罗来纳州立大学兽医院纳入研究。
阿糖胞苷以 50mg/m2/h 的速率经奥姆尼泊德系统作为 SC 持续输注 8 小时。在输注开始后 0、4、6、8、10、12 和 14 小时采集血浆样本。通过高压液相色谱法测量血浆阿糖胞苷浓度。采用非线性混合效应方法生成群体药代动力学参数估算值。
平均峰浓度（Cmax）为 7510ng/ml（范围 50409690ng/ml；SD 1912.41ng/ml），平均达峰时间为 7 小时（范围 48 小时；SD 1.67 小时），半衰期为 1.13 小时（SD 0.29 小时），曲线下面积均值为 52996.82 小时×μg/ml（范围 35963.67~71848.37 小时×μg/ml；SD 12960.90 小时×μg/ml）。所有犬在 4、6、8 和 10 小时时间点的 Cmax 浓度均超过 1000ng/ml（1.0μg/ml）。
奥姆尼泊德系统 SC 持续输注阿糖胞苷在犬中是可行的，能够在阿糖胞苷给药后 410 小时达到稳定浓度超过 1μg/ml，Cmax 为 7510ng/ml（范围 50409690ng/ml；SD 1912.41ng/ml）。这些与先前在健康研究比格犬和病因不明的脑膜脑脊髓炎患犬中经 IV 持续输注方式给予阿糖胞苷的报道值相当。
