Lidocaine distribution into the CNS following nasal and arterial delivery: a comparison of local sampling and microdialysis techniques

Abstract

The disposition of lidocaine within the CNS of the rat following nasal and intra-arterial delivery was characterized using a microdialysis technique. Lidocaine concentrations in the cisterna magna were determined using microdialysis and compared to those previously determined using a direct CSF sampling method. The disposition profiles for lidocaine into the cisternal CSF obtained using microdialysis were found to be similar to those obtained by direct CSF sampling techniques over an initial 120-min interval. In other experiments, lidocaine disposition in the right (dosed side) and left olfactory bulb following nasal (i.n.) and intra-arterial (i.a.) administration was studied using microdialysis. The lidocaine concentrations in the ipsilateral olfactory bulb were slightly higher after drug administration into the nasal cavity than those in the contralateral olfactory bulb over the initial 20-min sampling interval. Drug concentrations found in the right olfactory bulb were not significantly different from those found in the left olfactory bulb following intra-arterial administration. Comparisons of lidocaine disposition in the right olfactory bulb and cerebellum, two CNS sites with the same regional vascular supply, showed that the disposition patterns were nearly identical for the two sites following i.a. administration. There was a significant lengthening in the t max at both sites following i.n. delivery compared to i.a. delivery, and the relative concentrations at each site were no longer equivalent. From these results, it appears that the microdialysis technique is a useful tool for studying drug distribution into the CNS. The changes in disposition patterns between i.a. and i.n. administration indicate that other factors or pathways, in addition to the systemic circulation, play a role in the transport of lidocaine into the brain following nasal administration.