Pupillometry in healthy volunteers as a biomarker of tramadol efficacy

Summary What is known and Objective: The opioid effect of tramadol, which can be detected by pupillary response, is predominantly mediated by the O‐demethylated metabolite, formed via CYP2D6. This study was designed to evaluate the effects of tramadol using different parameters of pupillometry as biomarkers. Methods: Sixty‐nine healthy volunteers received tramadol hydrochloride drops orally at a dose of 0·7 mg/kg. Pre‐dose and 2‐h post‐dose pupillometric measurements were performed. The polymorphism of CYP2D6 was analysed. Results and Discussion: Large interindividual variability was observed in the tramadol‐induced pupillary reaction. Miosis was induced in 69·6% and mydriasis in 30·4% of the subjects. The pupillary response differed in relation to the CYP2D6 genotype. A maximal difference in initial pupil diameter of 0·81 mm was found in extensive metabolizers. There were significant effects observed on the pupillary light reflex parameters with tramadol administration (P