In vitro versus canine data for predicting input profiles of isosorbide-5-mononitrate from oral extended release products on a confidence interval basis.

The objective of this study was to assess the relative usefulness of in vitro and canine data sets in the prediction of input rates of isosorbide-5-mononitrate (ISMN) from extended release (ER) products on a confidence interval basis. ISMN is a highly soluble compound with high permeability in the upper GI tract but not in the colon. Two ISMN ER tablet formulations were studied: Imdur and an osmotic pump. Differences between amount of drug absorbed versus time predicted from in vitro and canine data and results observed in humans were assessed using the estimated median value of the difference factor, f(1), and its associated 90% bootstrap confidence intervals. For both products, median f(1) values and their associated confidence intervals for the comparisons between in vitro and human profiles and between canine and human profiles were similar. Although the median difference between the human input profiles of the two ISMN ER products was equally well predicted by in vitro and canine data, the 90% confidence intervals for this difference were better predicted by the canine data.