Evrard P A, Cumps J, Verbeeck R K
Pharmacokinetics Laboratory, Catholic University of Louvain, Brussels, Belgium.
Pharm Res. 1996 Jan;13(1):18-22. doi: 10.1023/a:1016008712756.
The in vivo plasma protein binding and pharmacokinetics of flurbiprofen were studied in awake, unrestrained rats using intravenous microdialysis sampling.
Flurbiprofen (20 mg/kg) was administered i.v. to 2 groups of 6 rats: in both groups sampling was carried out by microdialysis, but in the second group an additional 10 blood samples were withdrawn via a jugular cannula. In vitro and ex vivo (following i.v. administration of flurbiprofen 20 mg/kg to another group of 13 rats) plasma protein binding of the drug was determined by equilibrium dialysis.
The area under the unbound plasma concentration-time profile of flurbiprofen (AUCu), determined by microdialysis sampling was somewhat smaller (-19%, p = 0.666) in the rats undergoing simultaneous serial blood sampling (2.21 +/- 0.36 micrograms.h/ml) as compared to the rats undergoing microdialysis sampling only (2.73 +/- 0.60 micrograms.h/ml). Comparison of total and unbound concentrations of flurbiprofen showed an in vivo plasma binding varying between 99.5% at low and 98.0% at high total flurbiprofen plasma concentrations. Plasma binding of flurbiprofen determined in vitro over the same concentration range was higher (99.5-99.9%) but also concentration-dependent. Plasma binding of flurbiprofen determined ex vivo, on the other hand, corresponded well with the in vivo binding.
Monitoring the fraction of drug unbound in blood of an individual rat throughout a pharmacokinetic experiment has now become possible by using simultaneous sampling of blood and intravenous microdialysates.
采用静脉微透析采样技术，在清醒、自由活动的大鼠体内研究氟比洛芬的血浆蛋白结合率和药代动力学。
将氟比洛芬（20mg/kg）静脉注射给两组各6只大鼠：两组均通过微透析进行采样，但第二组还通过颈静脉插管额外采集10份血样。通过平衡透析法测定药物在体外（另一组13只大鼠静脉注射20mg/kg氟比洛芬后）和体内（给药后）的血浆蛋白结合率。
通过微透析采样测定，同时进行系列血样采集的大鼠中氟比洛芬的非结合血浆浓度-时间曲线下面积（AUCu）（2.21±0.36μg·h/ml），与仅进行微透析采样的大鼠相比略小（-19%，p = 0.666）（2.73±0.60μg·h/ml）。氟比洛芬总浓度和非结合浓度的比较显示，体内血浆结合率在氟比洛芬血浆总浓度低时为99.5%，高时为98.0%之间变化。在相同浓度范围内体外测定的氟比洛芬血浆结合率较高（99.5 - 99.9%），但也呈浓度依赖性。另一方面，体内测定的氟比洛芬血浆结合率与体外测定结果相符。
通过同时采集血液和静脉微透析液，现在有可能在整个药代动力学实验过程中监测个体大鼠血液中未结合药物的比例。
