Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism for gastroesophageal reflux responsible for gastroesophageal reflux disease (GERD). Evaluation of compounds to reduce TLESRs is done through summary exposure [pharmacokinetic (PK)] and response [pharmacodynamic (PD)] measures. Plan et al. evaluated PK/PD models for treating TLESRs using either count data or repeated time-to-event (RTTE) data and compared the ability of these models to characterize the system and drug characteristics. The repeated time-to-event is a very novel and powerful approach, and this is the first publication with RTTE that is applied to experimental data. The comparison of the RTTE approach with the standard count approach highlights the shortcomings of the current standard approach to evaluate TLESRs. The simulation tools that resulted from this model-based approach provide subtle insight into experimental design issues by probing the system further. These studies demonstrate that modeling approaches for assessing treatment of GERD using count or RTTE data linked to a dynamic PK/PD representation of exposure are superior to using summary PK and PD measures and are associated with a higher power to detect a statistically significant drug effect.
See article at J Pharmacol Exp Ther 2011, 339:878–885.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics