RAPID CLEARANCE OF METHYLPREDNISOLONE AFTER INTRATYMPANIC APPLICATION IN HUMANS. COMMENT ON: BIRD PA, BEGG EJ, ZHANG M, ET AL. INTRATYMPANIC VERSUS INTRAVENOUS DELIVERY OF METHYLPREDNISOLONE TO COCHLEAR PERILYMPH. OTOL NEUROTOL 2007;28:1124-30

The study by Bird and co-authors (1) is extremely important to the field of drug delivery to the inner ear as it provides the first measurements of human perilymph levels of a glucocorticoid (methylprednisolone, MP) following local intratympanic application. Perilymph samples were taken at various times (20 min to 3 hrs) after application and the measurements tabulated. However, because of the variability they observed, the authors chose to pool their data which were presented as a simple scatterplot. We re-analyzed the raw data taking into account the timing of the samples, from which we have been able to derive important pharmacokinetic parameters for MP entry into the inner ear. The symbols in Figure 1 show Bird et al.’s data replotted based on the sample timing information. It is apparent that samples taken at 1 hour show consistently higher levels than samples taken at longer times (2 hrs, 3 hrs) that are uniformly low. We have used computer simulation methods (2) to calculate expected sample concentration time courses as kinetic parameters were varied. The most important variable affecting the time course is the rate of drug clearance from the system. The rate of clearance was varied while calculating the sum of squares of deviations between calculated sample values and those obtained experimentally. The lowest sum of squares, indicating best fit, was found with a clearance half-time of 27 min. This estimated rate of clearance for MP was somewhat faster than that calculated for prednisolone based on prior experiments in guinea pigs, which occurred with a half-time of 130 min (2;3).