Anatomic localization of topically applied [14C]penicillin during experimental focal epilepsy in cat neocortex

14C-labeled penicillin was topically applied to the suprasylvian gyri of adult cats in order to study the distribution of the convulsant agent at the onset of focal epileptogenesis. Using radioassay and autoradiographic techniques, a steep gradient of penicillin was found. At the time interictal EEG spike discharges appeared, 95% of the labeled drug was in the uppermost cortical layers (laminae I-III). Analysis of the concentration profiles obtained by scintillation counting showed that penetration of penicillin into brain occurs primarily by passive diffusion. An apparent diffusion coefficient for penicillin in neocortex of 1.5 sq. mm/h was calculated using modifications of standard diffusion equations. It is apparent that with a rapidly acting topical convulsant such as penicillin, the dimensions of the neuronal pool actually in contact with the drug will change significantly over time. The changing boundaries of the epileptic neuronal aggregate must be taken into account when interpreting observations made within and around such experimentally produced epileptic foci.