Evrard-PA; Deridder-G; Verbeeck-RK
Pharm-Res. 1996 Jan; 13(1): 12-7
PURPOSE. A flexible microdialysis probe was designed for intravenous
sampling 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 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. RESULTS. 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.
CONCLUSIONS. 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.
AN: 96221671