Watanabe Takaho, Schulz Daniela, Morisseau Christophe, Hammock Bruce D
Department of Entomology and UCD Cancer Center, University of California, One Shields Avenue, Davis, CA 95616, USA.
Anal Chim Acta. 2006 Feb 10;559(1):37-44. doi: 10.1016/j.aca.2005.11.049.
A method for pharmacokinetic studies using cassette dosing associated with serial bleeding in mice is described. PK profiles of four soluble epoxide hydrolase inhibitors were determined following oral, subcutaneous or intraperitoneal administration individually or in cassette dosing. Parent analyses were performed on only 5 microL of whole blood from serial bleeds (up to 10 per animal), by LC/MS/MS. An accuracy (88-100%) and precision (<10% RSD) were observed, leading to reliable datum points for PK calculation. PK profiles, T(max), C(max) and half-life values after cassette dosing were similar to the individual PK results. This method dramatically increases speed of data collection while dramatically reducing cost and animal usage. The results presented here clearly indicate that this proposed method could be applicable to high-throughput PK studies.
描述了一种使用盒式给药并结合小鼠连续采血进行药代动力学研究的方法。分别或采用盒式给药方式经口、皮下或腹腔注射后，测定了四种可溶性环氧化物水解酶抑制剂的药代动力学特征。通过液相色谱/串联质谱法，仅对连续采血（每只动物最多10次）获得的5微升全血进行母体分析。观察到准确度（88 - 100%）和精密度（相对标准偏差<10%），从而得到用于药代动力学计算的可靠数据点。盒式给药后的药代动力学特征、达峰时间（T(max)）、峰浓度（C(max)）和半衰期值与单独给药的药代动力学结果相似。该方法显著提高了数据收集速度，同时大幅降低了成本和动物使用量。此处给出的结果清楚地表明，所提出的这种方法可应用于高通量药代动力学研究。
