Evrard P A, Deridder G, Verbeeck R K
Pharmacokinetics Laboratory, School of Pharmacy, Catholic University of Louvain, Brussels, Belgium.
Pharm Res. 1996 Jan;13(1):12-7. doi: 10.1023/a:1016056628685.
A flexible microdialysis probe was designed for intravenous sampling in small laboratory animals.
Surgical techniques were developed to implant this probe via the femoral vein in the vena cava of the mouse and the rat. The in- and outlet of the probe were exteriorized above the tail of the animal and were directly connected to the microsyringe pump for perfusate delivery and to the injection valve for on-line HPLC analysis of the microdialysate samples.
The in vitro recoveries of flurbiprofen and naproxen for these probes were 68.2 +/- 6.9% (mean +/- S.D., n = 12) and 66.5 +/- 7.3%, respectively. The relatively loss by in vivo retrodialysis, measured the day after the implantation of the probes, was 66.1 +/- 8.8% for flurbiprofen and 60.9 +/- 9.9% for naproxen. The pharmacokinetics of unbound flurbiprofen were studied following i.v. bolus administration of flurbiprofen to the mouse (n = 4) and the rat (n = 6) with on-line HPLC analysis of microdialysates to unbound concentrations using the in vivo loss of flurbiprofen by retrodialysis carried out just before the start of the pharmacokinetic experiment. The integrity of the probe throughout the experiment was monitored by continuous retrodialysis of naproxen.
The developed techniques can be used to carry out routine pharmacokinetic studies in the mouse and the rat illustrated by our experiments with flurbiprofen, a compound with very high plasma protein binding.
设计一种灵活的微透析探针，用于在小型实验动物中进行静脉采样。
开发了手术技术，通过股静脉将该探针植入小鼠和大鼠的腔静脉。探针的进出口在动物尾巴上方引出，并直接连接到微量注射泵以输送灌注液，连接到进样阀以对微透析样品进行在线高效液相色谱分析。
这些探针的氟比洛芬和萘普生的体外回收率分别为68.2±6.9%（平均值±标准差，n = 12）和66.5±7.3%。在植入探针后的第二天测量，氟比洛芬和萘普生通过体内逆向透析的相对损失分别为66.1±8.8%和60.9±9.9%。在对小鼠（n = 4）和大鼠（n = 6）静脉推注氟比洛芬后，利用在药代动力学实验开始前通过逆向透析测定的氟比洛芬在体内的损失，通过在线高效液相色谱分析微透析液中未结合的浓度，研究了未结合氟比洛芬的药代动力学。通过萘普生的连续逆向透析监测整个实验过程中探针的完整性。
所开发的技术可用于在小鼠和大鼠中进行常规药代动力学研究，我们用氟比洛芬（一种血浆蛋白结合率非常高的化合物）进行的实验说明了这一点。
