Quantification of ethanol concentrations in the extracellular fluid of therat brain: In vivo calibration of microdialysis probes

Traditional microdialysis techniques provide qualitative data, although qua ntitative data are often required for pharmacodynamic analyses. This study evaluated a potentially useful in vivo delivery technique to calibrate micr odialysis probes for ethanol. We measured in vivo delivery extraction fract ions within subjects across 2 days and found no change over time. We tested the effect of diffusion direction on extraction fraction and found that it was higher for ethanol diffusion out of the probe than for diffusion into the probe, both in vitro and in vivo, The in vivo extraction fraction ratio of diffusion,, Versus diffusion(OUT) was 0.65 +/- 0.03. Finally, we predic ted extracellular brain ethanol concentrations after 1 g/kg ethanol adminis tration using in vivo delivery, "no net flux" dialysis, or in vivo delivery corrected for diffusion direction with the in vivo extraction fraction rat io. Both in vivo delivery and "no net flux" dialysis predicted brain concen trations that were approximately one-third lower than blood concentrations, whereas the corrected in vivo delivery predicted extracellular concentrati ons very similar to blood concentrations. We conclude that microdialysis ca libration methods for ethanol require a measure of extraction fraction for diffusion into the probe. Further studies are needed to establish whether t his effect is common to other alcohols.