Determination of the ED50 of Tegileridine and Comparison with Fentanyl for Analgesia During Hysteroscopy in Chinese Female Patients: An Exploratory Sequential Dose‑Finding Study

Objective: Tegileridine is a novel selective μ-opioid receptor agonist. This exploratory dose‑finding study aimed to estimate the 50% effective dose (ED50) and secondarily the 95% effective dose (ED95) of tegileridine for suppressing the cervical dilation reflex during hysteroscopic surgery under propofol anesthesia, compare it with fentanyl, and evaluate perioperative safety in an exploratory manner. Methods: This prospective, randomized, single‑center trial enrolled 54 patients (ASA I‑II). Patients received tegileridine (initial dose 16.67 μg/kg) or fentanyl (initial dose 2 μg/kg) with propofol. Doses were adjusted using the Dixon sequential method. The primary endpoint was ED50 with its 95% confidence interval (CI), estimated using the percentile bootstrap method (2,000 replicates) as the primary inferential framework. ED95 was calculated secondarily via probit regression. Safety data are reported descriptively. Results: Twenty‑seven patients per group completed the study. The bootstrap‑based ED50 for tegileridine was 23.22 μg/kg (95% CI: 22.39‑24.19); for fentanyl, 1.51 μg/kg (95% CI: 0.97‑4.07). The ED50 potency ratio (tegileridine:fentanyl) was approximately 1:15 (95% uncertainty range derived from bootstrap CIs: 1:5.5 to 1:24.9). The ED95 values from probit regression were 23.89 μg/kg (95% CI: 23.68‑24.12) for tegileridine and 1.97 μg/kg (95% CI: 1.87‑2.07) for fentanyl. Respiratory depression/hypoxemia was observed in 14.8% of the tegileridine group and 59.3% of the fentanyl group; these exploratory findings should be interpreted with caution given the small sample and open‑label design. Conclusion: This exploratory study estimated the ED50 of tegileridine and fentanyl for hysteroscopic surgery. The ED50-based potency ratio and the observed differences in safety outcomes require confirmation in larger, adequately powered, blinded trials. The ED95 estimates are model‑based and carry substantial uncertainty. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2500107995.