An overview of pharmacodynamic drug interaction with isobole and response surface model in anesthesia

ABSTRACT

Drug interaction is the principal concept of anesthetic practice. Typically, drug interactions are divided into three categories i.e., additive, synergistic, or infra-additive interactions. Pharmacodynamic drug interactions are typically described using mathematical models. The traditional model is an isobole, which is an iso-effect curve that shows dose or concentration combinations that result in equal effect. Response surface model is a pharmacodynamic tool that describes all isoboles and concentration effect curves for a given endpoint in one equation. In summarizing concentration-effect relationships, the response surface model allows anesthesiologists the versatility to work with precise and safe drug interactions. The aim of this review is to provide the reader with principal concepts of the isobole and response surface model and evaluate characteristics of most commonly used models, including 4 response surface models i.e., the Greco model, reduced Greco model, Minto model, and the Hierarchy model. In addition, the concept of population analysis using nonlinear mixed effects modeling is introduced.