Development of Microdialysis Probe Method for Partition Coefficient Determinationfor Pharmacokinetic Modeling

摘要

The value of any Physiologically Based Pharmacokinetic (PBPK) model dependslargely on the quality of the parameter estimates entered into the model. One of the critically important parameters requiring estimation is the partition coefficient. Commonly in the field of pharmacokinetics, partition coefficients are determined by the modified version of the vial equilibration technique. This method is an in vitro method in which an animal must be sacnficed, and the tissue and blood harvested to complete the procedure. In the vial equilibration technique, certain physiological aspects must be compromised as the tissues are isolated from a living system. However, a method to determine various partition coefficients in vivo would reduce or eliminate the compromises inherent in the in vitro approach. This technical report describes a method that was developed to determine in vivo partition coefficients by using microdialysis probes. If the microdialysis probe method of determining partition coefficients in vivo is shown to be valid, then it could be used in collaboration with the vial equilibration method to provide partition coefficients of better quality than is currently available. Therefore, the data produced by the pharmacokinetic models in which partition coefficients are used would be greatly enhanced.