PDF(Pubmed)
Abstract：
In vivo ultrafiltration has been used in veterinary pharmacokinetics since the early 2000\'s as an improvement on the tissue cage model which enables sampling of fluids from extra-circulatory compartments. Variability in analyte recovery from ultrafiltration samples, due to membrane fouling or tissue inflammation, has been a concern for this technique. Internal standards may be used to scale or verify the unknown result, such as is common in analytical extractions and in vivo microdialysis. Eight merino sheep were implanted with subcutaneous tissue cages and 2 weeks prior to the initiation of the study the sheep were injected with 0.2 mg/kg moxidectin subcutaneously. On the day of the study ultrafiltration probes were inserted subcutaneously. At time zero 4 mg/kg of carprofen was injected intravenously. Plasma, tissue cage, and ultrafiltration samples were taken 30 min before and 0.5, 1, 2, 3, 4, 5, 7, 24, 36, 48, 72 h after dosing. Carprofen and moxidectin concentrations were measured by LC-MS/MS. Pharmacokinetic parameters were estimated using Monolix for both the carprofen concentrations and the moxidectin corrected carprofen concentrations. The ultrafiltration probes failed to consistently produce enough sample volume to analyse. Moxidectin concentrations in the plasma and tissue cage fluid were stable throughout the 72 h sampling window. Moxidectin proved to be suitable as an in vivo internal standard for pharmacokinetic research using, tissue cages, plasma sampling and ultrafiltration probes, but the application of ultrafiltration techniques requires refinement.
摘要：
自2000年初以来，体内超滤已用于兽医药代动力学，作为对组织笼模型的改进，该模型可以从循环外隔室中采样流体。超滤样品中分析物回收率的变化，由于膜污染或组织炎症，一直是这项技术的关注点。内部标准可用于缩放或验证未知结果，例如在分析提取和体内微透析中常见。将八只美洲羊植入皮下组织笼，并在研究开始前2周皮下注射0.2mg/kg莫昔克丁。在研究当天,皮下插入超滤探针。在时间零时,静脉内注射4mg/kg卡洛芬。血浆,组织笼,和超滤样品在给药前30分钟和给药后0.5、1、2、3、4、5、7、24、36、48、72小时采集。通过LC-MS/MS测量卡洛芬和莫昔克丁的浓度。使用Monolix估计卡洛芬浓度和莫昔克丁校正的卡洛芬浓度的药代动力学参数。超滤探针不能一致地产生足够的样品体积以进行分析。在整个72小时的采样窗口中，血浆和组织笼液中的莫昔克星浓度是稳定的。莫昔克丁被证明适合作为药代动力学研究的体内内标，组织笼,血浆取样和超滤探头，但是超滤技术的应用需要改进。
