Liang Linda S, Wong Wesley, Burt Helen M
Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, British Columbia, Canada V6T 1Z3.
J Pharm Sci. 2005 Jun;94(6):1204-15. doi: 10.1002/jps.20341.
The pharmacokinetics and tissue distribution of methotrexate (MTX) were investigated following intra-articular injection of either MTX solution or controlled release MTX loaded microspheres in healthy rabbit joints. MTX solution or MTX loaded microspheres (size 30-100 mum) (10 mg MTX) was injected into the right knee joint cavity of rabbits. Blood samples were taken at predetermined times from the jugular vein. Urine samples were also collected over time periods up to 24 h. The major organs and synovial tissues were removed for analysis 6 and 24 h post-injection (n = 4). MTX and 7-OH-MTX concentrations in the plasma and major organs were determined by HPLC. The MTX plasma area under the concentration-time curve (AUC) for rabbits injected with MTX solution was seven fold higher than that of the rabbits injected with MTX microspheres, while t(1/2) and mean residence time (MRT) were not significantly different between two treatment groups. Four fold more MTX was excreted in the urine from rabbits injected with MTX solution compared to those injected with MTX loaded microspheres 24 h following intra-articular injection. The concentration of MTX in the synovial tissues following intra-articular injection was significantly higher in the rabbits injected with microspheres than in the rabbits injected with MTX solution. MTX solution was rapidly cleared from the joint cavity while MTX encapsulated microspheres retained MTX in the joint cavity.
在健康兔关节内注射甲氨蝶呤（MTX）溶液或载有MTX的控释微球后，研究了MTX的药代动力学和组织分布。将MTX溶液或载有MTX的微球（尺寸为30 - 100μm）（10mg MTX）注入兔的右膝关节腔。在预定时间从颈静脉采集血样。还在长达24小时的时间段内收集尿样。在注射后6小时和24小时取出主要器官和滑膜组织进行分析（n = 4）。通过高效液相色谱法测定血浆和主要器官中MTX和7 - OH - MTX的浓度。注射MTX溶液的兔的MTX血浆浓度 - 时间曲线下面积（AUC）比注射MTX微球的兔高7倍，而两个治疗组之间的t(1/2)和平均驻留时间（MRT）无显著差异。关节内注射24小时后，注射MTX溶液的兔尿中排出的MTX比注射载有MTX微球的兔多4倍。关节内注射后，注射微球的兔滑膜组织中MTX的浓度显著高于注射MTX溶液的兔。MTX溶液从关节腔中迅速清除，而包裹MTX的微球将MTX保留在关节腔中。
