Pupillometry in healthy volunteers as a biomarker of tramadol efficacy

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 < 0.05) except for the reflex amplitude and constriction velocity. What is new and Conclusion: The pharmacodynamic effects of tramadol were easily detected using both static and dynamic pupil parameters. The pharmacodynamic profiles were markedly influenced by the CYP2D6 phenotype.