Individualized Dosing With Anesthetic Agents

Abstract

The development of fundamental pharmacokinetics and pharmacodynamics concepts has enabled anesthesiologists to choose and dose anesthetic agents on a rational basis. The application of these concepts to a variety of clinical scenarios and patient populations makes it possible to individualize the dose, thereby decreasing the risk of complications. As more knowledge is gained about the sometimes profound differences in drug response, empirical dosing such as in milligrams per kilogram of total body weight is disappearing from the anesthesia specialty.

Modeling the Influence of the A118G Polymorphism in the OPRM1 Gene and of Noxious Stimulation on the Synergistic Relation between Propofol and Remifentanil

“…Drug Combination. The BIS versus time data were analyzed first using the empirical interaction model presented in Equation (6). In that first model, intersubject variability was included on BIS 0 , EC 50 , Prop , k e0 , Prop .…”

“…But the influence of genetic variability in drug dosing of anesthetic drugs has not been widely studied. 6 The OPRM1 gene encodes the μ-opioid receptor, which is a member of the G protein-coupled receptor family. 7 Genetic variations in exon 1 of the OPRM1 gene, located at chromosome 6, have been associated with changes in the spatial conformation of the μ-opioid receptor as a result of amino acid changes in the receptor protein and thereby altering its function.…”

Pharmacogenomics in Early-Phase Clinical Development

“…A twin study of dicumarol pharmacokinetics provided the first evidence of genetic-based pharmacokinetics [23]. Another example of a PGx-guided individualized intervention that may not be thought of as such but has been practiced for decades is anesthesia, where the doses of the anesthetics are continuously adapted to the individual’s signs and symptoms [24]. …”

Achieving the Promise of Personalized Medicine

“…Despite this information, there are no dosing algorithms for methotrexate for treatment of rheumatoid arthritis. In contrast to the other examples, Lemmens and Stanski 22 describe anesthesia as the ultimate example of personalized medicine because the anesthesiologist is constantly assessing the patient's wakefulness and adjusting the dose.…”