ArticleCPT: pharmacometrics & systems pharmacology2022
Semimechanistic models to relate noxious stimulation, movement, and pupillary dilation responses in the presence of opioids.
Article in CPT: pharmacometrics & systems pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 4 citations in OpenAlex.
- Age‑stratified median effective dose (ED₅₀) of remimazolam besylate for successful gastroscope insertion without body movement in geriatric patients.BMC anesthesiology · 2026Article
- Semimechanistic models to relate noxious stimulation, movement, and pupillary dilation responses in the presence of opioids.CPT: pharmacometrics & systems pharmacology · 2022Article
- Quantitative approaches to drug safety: The 2022 PSP special issue.CPT: pharmacometrics & systems pharmacology · 2022Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intraoperative targeting of the analgesic effect still lacks an optimal solution. Opioids are currently the main drug used to achieve antinociception, and although underdosing can lead to an increased stress response, overdose can also lead to undesirable adverse effects. To better understand how to achieve the optimal analgesic effect of opioids, we studied the influence of remifentanil on the pupillary reflex dilation (PRD) and its relationship with the reflex movement response to a standardized noxious stimulus. The main objective was to generate population pharmacodynamic models relating remifentanil predicted concentrations to movement and to pupillary dilation during general anesthesia. A total of 78 patients undergoing gynecological surgery under general anesthesia were recruited for the study. PRD and movement response to a tetanic stimulus were measured multiple times before and after surgery. We used nonlinear mixed effects modeling to generate a population pharmacodynamic model to describe both the time profiles of PRD and movement responses to noxious stimulation. Our model demonstrated that movement and PRD are equally depressed by remifentanil. Using the developed model, we changed the intensity of stimulation and simulated remifentanil predicted concentrations maximizing the probability of absence of movement response. An estimated effect site concentration of 2 ng/ml of remifentanil was found to inhibit movement to a tetanic stimulation with a probability of 81%.
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