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.