LIDOCAINE DISTRIBUTION INTO THE CNS FOLLOWING NASAL AND ARTERIAL DELIVERY - A COMPARISON OF LOCAL SAMPLING AND MICRODIALYSIS TECHNIQUES

The disposition of lidocaine within the CNS of the rat following nasal and intra-arterial delivery was characterized using a microdialysis t echnique. Lidocaine concentrations in the cisterna magna were determin ed using microdialysis and compared to those previously determined usi ng a direct CSF sampling method. The disposition profiles for lidocain e into the cisternal CSF obtained using microdialysis were found to be similar to those obtained by direct CSF sampling techniques over an i nitial 120-min interval. In other experiments, lidocaine disposition i n the right (dosed side) and left olfactory bulb following nasal (i.n. ) and intra-arterial (i.a.) administration was studied using microdial ysis. The lidocaine concentrations in the ipsilateral olfactory bulb w ere slightly higher after drug administration into the nasal cavity th an those in the contralateral olfactory bulb over the initial 20-min s ampling interval. Drug concentrations found in the right olfactory bul b were not significantly different from those found in the left olfact ory bulb following intra-arterial administration. Comparisons of lidoc aine disposition in the right olfactory bulb and cerebellum, two CNS s ites with the same regional vascular supply, showed that the dispositi on patterns were nearly identical for the two sites following i.a. adm inistration. There was a significant lengthening in the t(max) at both sites following i.n. delivery compared to i.a. delivery, and the rela tive 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 dispositi on patterns between i.a. and i.n. administration indicate that other f actors or pathways, in addition to the systemic circulation, play a ro le in the transport of lidocaine into the brain following nasal admini stration. (C) 1998 Elsevier Science B.V. All rights reserved.