INTRAVENOUS MICRODIALYSIS IN THE MOUSE AND THE RAT - DEVELOPMENT AND PHARMACOKINETIC APPLICATION OF A NEW PROBE

Purpose. A flexible microdialysis probe was designed for intravenous s ampling in small laboratory animals. Methods. 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 exteri orized above the tail of the animal and were directly connected to the microsyringe pump for perfusate delivery and to the injection valve f or on-line HPLC analysis of the microdialysate samples. Results. The i n 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. T he relative 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 th e mouse (n=4) and the rat (n=6) with on-line HPLC analysis of microdia lysates every 10 minutes during 6 to 8 hours. Flurbiprofen microdialys ate concentrations were converted 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 prob e throughout the experiment was monitored by continuous retrodialysis of naproxen. Conclusions. The developed techniques can be used to carr y out routine pharmacokinetic studies in the mouse and the rat as illu strated by our experiments with flurbiprofen, a compound with very hig h plasma protein binding.